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KR20210116712A - 말라리아 백신 - Google Patents

말라리아 백신 Download PDF

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KR20210116712A
KR20210116712A KR1020217029655A KR20217029655A KR20210116712A KR 20210116712 A KR20210116712 A KR 20210116712A KR 1020217029655 A KR1020217029655 A KR 1020217029655A KR 20217029655 A KR20217029655 A KR 20217029655A KR 20210116712 A KR20210116712 A KR 20210116712A
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류지 우에노
와타루 아카하타
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Abstract

본 발명은 폴리펩티드 및 하나 이상의 말라리아 항원을 포함하는 입자, 및 이를 포함하는 조성물 또는 백신, 약제에서의, 특히 말라리아 감염의 예방 또는 치료에서의 이의 용도를 제공한다.

Description

말라리아 백신 {MALARIA VACCINE}
본 발명은 폴리펩티드 및 하나 이상의 말라리아 항원을 포함하는 입자, 및 이를 포함하는 조성물 또는 백신, 약제에서의, 특히 말라리아의 예방 또는 치료에서의 이의 용도에 관한 것이다.
말라리아는 연간 약 2 억 5 천만 건의 발병사례 및 100 만 건의 사망사례가 발생하는, 세계적으로 가장 유행하는 중증 감염성 질환 중 하나이다 (WHO, 2009). 사망자는 주로 5 세 미만의 아동 및 임신한 여성에서 존재한다. 매 45 초마다, 아프리카 아동이 말라리아로 사망하고 있다. 상기 질환은 감염된 모기에 의해 사람에서 사람으로 전염되기 때문에, 과거의 근절 활동에는 대량의 살충제 사용이 포함되었다. 이러한 살충제의 사용은, 예를 들어 미국 남동부에서 성공을 거두었지만, 대부분의 개발이 낙후된 열대 지역에서는 실패하였다. 현재의 활동에는 베드넷 (bednet), 특히 살충제가 주입된 베드넷을 분포하여, 밤에 모기 물림을 예방하는 것이 포함된다. 하지만, 예방 및 치료 둘 모두를 위한 살충제 및 항-말라리아 약물에 대한 내성이 급속하게 증가하고 있다. 따라서, 이러한 질환으로부터 수백만의 사람들을 보호하기 위한 말라리아 백신이 반드시 필요하다 (http://www.globalvaccines.org/content/malaria+vaccine+program/19614).
열대열 말라리아 원충 (Plasmodium falciparum) 에 의해 야기되는 말라리아는, 특히 아프리카의 아동 및 임신한 여성에서 주요한 공중 보건 위협으로 남아있다. 효과적인 말라리아 백신은 질환 부담을 감소시키는 유용한 도구일 수 있으며, 세계의 일부 지역에서의 말라리아 근절에 기여할 수 있다. 현재 말라리아 백신 후보는 기생충 생활사 중 인간 및 모기 단계에 대한 것에 주목되어 왔으나, 지금까지, 비교적 적은 단백질이 가능한 백신 개발을 위해 연구되어 왔다.
가장 진보된 백신 후보, RTS,S 는 임상 2 상 시험에서 말라리아에 대한 부분적 보호를 제공하였고, 현재 아프리카에서 3 상 시험 평가 중이다 (The Journal of Clinical Investigation 120(12) 4168-4178, 2010).
CSP 는 포자소체 (sporozoite) 상의 지배적인 표면 항원이다. CSP 는 헤파린 술페이트 프로테오글리칸 (RI) 을 결합하는 N-말단 영역, 4 개-아미노산 (NPNA) 반복을 함유하는 중앙 영역, 및 트롬보스폰딘-유사 도메인 (RII) 을 함유하는 GPI-고정 C-말단 영역으로 이루어진다. RTS,S 백신에 포함된 CSP 의 영역은 마지막 16 회의 NPNA 반복 및 전체적인 측면 (flanking) C-말단을 포함한다. HBsAg 입자는 RTS,S 의 매트릭스 담체로서 간주되며, 이의 25% 는 CSP 분절과 융합된다 (The Journal of Clinical Investigation 120(12) 4168-4178, 2010).
RTS,S 에 대한 일련의 임상 2 상 시험에서, RTS,S 로 면역화된 말라리아에 감염된 적 없는 (malaria-naive) 성인의 30%-50% 가 상동 열대열 말라리아 원충 (P. falciparum) 클론에 감염된 모기에 의한 주입으로부터 보호되었다. 잠비아 및 케냐에서의 2 상 필드 시험에서, RTS,S 는 약 35% 의 성인에서 말라리아 감염에 대한 단기 보호를 제공하였지만, 케냐 시험의 결과는 통계적 유의성에 이르지 못했다. 모잠비크, 탄자니아 및 케냐에서의 수행된 2 상 시험에서, RTS,S 로 면역화된 아동 및 영유아의 약 30%-50% 가 임상 말라리아로부터 보호되었지만, 보호는 대체로 단기간이었다 (The Journal of Clinical Investigation 120(12) 4168-4178, 2010). 2012 년 11 월 9 일자, 온라인으로, New England Journal of Medicine (NEJM) 에 공개된, 중추적인, 대규모 3 상 시험의 결과는, RTS,S 말라리아 백신 후보가 말라리아에 대항하여 아프리카 영유아를 보호하는데 도움이 될 수 있음을 나타냈다. 대조군 백신으로의 면역화와 비교시, RTS,S 로 면역화된 영유아 (1차 백신접종 시 6-12 주된) 에서는 임상적 및 중증 말라리아 둘 모두에 있어서 1/3 적은 사례가 발생되었고, 주사에 대한 반응은 유사하였다.
현재는 말라리아에 대한 허가된 백신이 존재하지 않는다. 매우 효과적인 말라리아 백신이 간절히 요구된다.
바이러스-유사 입자 (VLP) 는 본래의 순수한 바이러스의 조직 및 형태를 모방하고 있지만, 바이러스 게놈은 포함하지 않는 다중단백질 구조로서, 가능성있는 보다 안전하고 저렴한 백신 후보로서 여겨진다. 소수의 예방용 VLP-계 백신이 현재 전 세계적으로 시판되고 있다: GlaxoSmithKline 사의 Engerix® (B 형 간염 바이러스) 및 Cervarix® (인간 유두종바이러스), 및 Merck and Co., Inc. 사의 Recombivax HB® (B 형 간염 바이러스) 및 Gardasil® (인간 유두종바이러스) 가 일부 예이다. 기타 VLP-계 백신 후보, 예컨대 인플루엔자 바이러스, 파르보바이러스 (parvovirus), 노르워크 (Norwalk) 및 각종 키메라 VLP 가 임상 시험 또는 전임상 평가 중에 있다. 다수의 기타 후보가 전임상 시험에서 성공하였음에도 불구하고, 여전히 소규모 기초 연구에 제한되어 있다. 대규모 VLP 제조의 결과는 공정 제어, 모니터링화 및 최적화의 측면에서 논의되고 있다. 따라서, 주요 업- 및 다운-스트림 기술적 시도가 확인 및 논의되고 있다. 성공적인 VLP-계 백신 블록버스터가, 임상 시험으로부터의 최신 결과 및 치료적 또는 예방적 백신을 위한 키메라 VLP-계 기술에 있어서의 최근의 발전과 함께 부수적으로 간략하게 제시되어 있다 (Expert Rev. Vaccines 9(10), 1149-1176, 2010).
치쿤군야 (Chikungunya) 바이러스 (CHIKV) 는, 이의 알파바이러스가 2004 년 케냐에서 재출현한 이후, 아프리카, 유럽 및 아시아에서 수백만명의 사람들을 감염시켜왔다. 상기 질환의 심각성 및 이러한 전염성 바이러스의 확산은 백신 또는 항바이러스성 치료제의 부재 하에서 심각한 공중 보건 위협을 야기한다. 전염성 치쿤군야 바이러스에 대한 VLP 백신이 감염에 대항하여 비(非)인간 영장류를 보호하는 것으로 보고되었다 (Nat Med. 2010 March; 16(3): 334-338). 미국 특허 공보 번호 2012/0003266 에는, 감염 또는 이의 하나 이상의 증상에 대한 면역을 유도하는 치쿤군야에 대한 백신 또는 항원 조성물의 제형화에 유용한, 하나 이상의 치쿤군야 바이러스 구조 폴리펩티드를 포함하는 바이러스-유사 입자 (VLP) 가 개시되어 있다. WO2012/106356 에는 개질된 알파바이러스 또는 플라비바이러스 (flavivirus) 바이러스-유사 입자 (VLP), 및 알파바이러스 및 플라비바이러스-매개 질환의 예방 또는 치료에 사용하기 위한 개질된 VLP 의 제조를 증진시키는 방법이 개시되어 있다 (상기 언급된 문헌은 본원에 참조로서 인용된다).
발명의 요약
제 1 양태에서, 본 발명은 폴리펩티드 및 하나 이상의 말라리아 항원을 포함하는 자가-조립 가능한 입자로서, 상기 폴리펩티드는 하나 이상의 제 1 부착 부위를 포함하고, 상기 하나 이상의 말라리아 항원은 하나 이상의 제 2 부착 부위를 포함하며, 상기 폴리펩티드 및 상기 말라리아 항원은 상기 하나 이상의 제 1 및 상기 하나 이상의 제 2 부착 부위를 통해 연결되는 입자를 제공한다.
제 2 양태에서, 본 발명은 본 발명의 제 1 양태에서 제공된 입자의 발현을 위해 고안된 핵산 분자를 제공한다.
제 3 양태에서, 본 발명은 본 발명의 제 1 양태에서 제공된 입자 및/또는 본 발명의 제 2 양태에서 제공된 핵산 분자를 포함하는 조성물 또는 백신을 제공한다.
제 4 양태에서, 본 발명은 본 발명의 제 1 양태에서 제공된 입자 및/또는 본 발명의 제 2 양태에서 제공된 핵산 분자를 포유류에 접촉시키는 것을 포함하는, 항체 제조 방법을 제공한다.
제 5 양태에서, 본 발명은 본 발명의 제 3 양태에서 제공된 조성물을 포유류에게 투여하는 것을 포함하는, 포유류에서의 면역조절 방법, 말라리아 치료 방법, 말라리아 항원에 대한 면역 반응 유도 및/또는 증진 방법을 제공한다.
제 6 양태에서, 본 발명은 본 발명의 제 4 양태에서 제공된 항체를 포유류에게 투여하는 것을 포함하는, 말라리아-유발 병원체에 대한 수동 면역 방법을 제공한다.
제 7 양태에서, 본 발명은 본 발명의 제 1 양태에서 제공된 입자 및/또는 본 발명의 제 2 양태에서 제공된 핵산 분자를 포유류에 접촉시키는 것을 포함하는, 대식세포 상에의 항원 제시 방법을 제공한다.
제 8 양태에서, 본 발명은 본 발명의 제 1 양태에서 제공된 입자의 제조 방법으로서, 상기 입자의 발현을 위해 고안된 벡터를 제조하고; 상기 벡터로 트랜스펙션된 세포를 배양하여 상기 입자를 발현시키고; 상기 입자를 회수하는 것을 포함하는 방법을 제공한다.
도 1 은 pVLP74_15 (VLP_CHI 532 NPNAx6) 벡터를 나타낸다.
도 2 는 pVLP78_15 (VLP_CHI 532 NPNAx25) 벡터를 나타낸다.
도 3 은 pVLP74_25 (VLP_VEEV 519 NPNAx6) 벡터를 나타낸다.
도 4 는 말라리아 VLP 로 면역화된 각각의 원숭이 혈청이 2 주 후 CSP 에 대한 항체의 고 역가를 유도했다는 것을 나타낸다.
도 5 는 도 4 에 제시된 데이터의 평균값 및 표준편차 (SD) 를 나타낸다.
도 6 은 CSP 에 대한 항체의 유도에 대한, CHIKV VLP 및 VEEV VLP 의 조합된 면역화의 효과를 나타낸다. 도면에서, Adj 는 보조제 (adjuvant) 를 나타낸다.
도 7 은 CSP 에 대한 항체의 유도에 대한, 말라리아 항원과 융합되지 않고 투여된 VLP 의 효과를 나타낸다. 도면에서, 4w, 6w, 10w 및 14w 는, 각각 면역화 후 4 주차, 면역화 후 6 주차, 면역화 후 10 주차 및 면역화 후 14 주차를 나타낸다.
도 8 은 CSP 에 대한 항체의 유도에 대한, 말라리아 항원과 융합되어 투여된 VLP 의 효과를 나타낸다. 도면에서, 4w, 6w, 10w 및 14w 는, 각각 면역화 후 4 주차, 면역화 후 6 주차, 면역화 후 10 주차 및 면역화 후 14 주차를 나타낸다.
도 9 는 CSP 에 대한 항체의 유도에 대한, 보조제 및 말라리아 항원과 융합되어 투여된 VLP 의 효과를 나타낸다. 도면에서, 4w, 6w, 10w 및 14w 는, 각각 면역화 후 4 주차, 면역화 후 6 주차, 면역화 후 10 주차 및 면역화 후 14 주차를 나타낸다.
도 10 은 실험 스케쥴을 나타낸다.
도 11 은 PCR 을 이용한 18S 말라리아 DNA 의 검출을 나타낸다.
(1) 폴리펩티드 및 하나 이상의 말라리아 항원을 포함하는 입자
제 1 양태에서, 본 발명은 폴리펩티드 및 하나 이상의 말라리아 항원을 포함하는 자가-조립 가능한 입자로서, 상기 폴리펩티드는 하나 이상의 제 1 부착 부위를 포함하고, 상기 하나 이상의 말라리아 항원은 하나 이상의 제 2 부착 부위를 포함하며, 상기 폴리펩티드 및 상기 말라리아 항원은 상기 하나 이상의 제 1 및 상기 하나 이상의 제 2 부착 부위를 통해 연결되는 입자를 제공한다.
본원에 사용된 바, "자가-조립 가능한 입자" 는 자발적으로 조립되는 하나 이상의 구성성분으로 형성된 입자를 지칭한다. 상기 구성성분은 폴리펩티드 또는 비(非)펩티드 화합물일 수 있다. 일 구현예에서, "자가-조립 가능한 입자" 는 하나 이상의 폴리펩티드를 포함하거나 또는 이로 이루어진 입자일 수 있다. 하나 이상의 폴리펩티드는 1 종 이상의 펩티드로 이루어진다. 일 구현예에서, 상기 입자는 10nm 이상, 예를 들어, 20nm 이상, 바람직하게는 50nm 이상의 직경을 갖는다. 일 구현예에서, 상기 입자의 분자량은 100 kDa 내지 100,000 kDa, 바람직하게는 400kDa 내지 30,000kDa 이다.
본 발명에 사용되는 폴리펩티드는 자발적으로 조립될 수 있다. 상기 폴리펩티드는 바이러스 구조 폴리펩티드일 수 있다. 따라서, 본 발명에 의해 제공되는 입자는 바이러스 유사 입자일 수 있다.
바이러스 구조 폴리펩티드는 자연 발생 바이러스 폴리펩티드 또는 이의 개질된 폴리펩티드일 수 있다. 일 구현예에서, 개질된 폴리펩티드는 캡시드 및 외피 단백질을 포함하는 자연 발생 바이러스 구조 폴리펩티드와 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 이상의 아미노산 서열 동일성을 갖는다. 일 구현예에서, 개질된 폴리펩티드는, 캡시드 및 외피 단백질을 포함하는 자연 발생 바이러스 구조 폴리펩티드에서, 최대 10% 의 아미노산이 제거, 치환 및/또는 첨가된 돌연변이이다.
일 구현예에서, 본 발명에 사용되는 바이러스 구조 폴리펩티드는 캡시드 및/또는 외피 단백질 또는 이의 단편으로 이루어지거나 또는 이를 포함한다. 예를 들어, 본 발명에 사용되는 바이러스 구조 폴리펩티드는 캡시드, 및 E2 및 E1 로 이루어지거나 또는 이를 포함한다.
항원은 E2 내에 삽입될 수 있다. 일 구현예에서, 본 발명의 제 1 양태에 의해 제공된 입자는 240 종의 캡시드, 240 종의 E1 단백질 및 240 종의 E2 단백질을 조립함으로써 형성될 수 있고, 여기서 말라리아 항원은 각각의 E2 단백질에 삽입된다.
본 발명에 사용되는 바이러스 구조 폴리펩티드는 알파바이러스 또는 플라비바이러스에서 유래될 수 있다. 따라서, 본 발명에 의해 제공되는 입자는 알파바이러스 또는 플라비바이러스 유래의 바이러스 유사 입자일 수 있다.
알파바이러스 및 플라비바이러스의 예에는, 비제한적으로, 아우라 (Aura) 바이러스, 바반키 (Babanki) 바이러스, 바마 포레스트 (Barmah Forest) 바이러스 (BFV), 베바루 (Bebaru) 바이러스, 카바쏘우 (Cabassou) 바이러스, 치쿤군야 (Chikungunya) 바이러스 (CHIKV), 동부 말뇌염 (Eastern equine encephalitis) 바이러스 (EEEV), 에일랏 (Eilat) 바이러스, 에버글라데스 (Everglades) 바이러스, 포트 모건 (Fort Morgan) 바이러스, 게타 (Getah) 바이러스, 하이랜드 제이 (Highlands J) 바이러스, 키지라가크 (Kyzylagach) 바이러스, 마야로 (Mayaro) 바이러스, 메 트리 (Me Tri) 바이러스, 미델부르크 (Middelburg) 바이러스, 모쏘 다스 페드라스 (Mosso das Pedras) 바이러스, 무캄보 (Mucambo) 바이러스, 엔두무 (Ndumu) 바이러스, 오녕녕 (O'nyong-nyong) 바이러스, 픽수나 (Pixuna) 바이러스, 리오 네그로 (Rio Negro) 바이러스, 로스 리버 (Ross River) 바이러스 (RRV), 연어 췌장 질환 바이러스, 셈리키 포레스트 (Semliki Forest) 바이러스, 신드비스 (Sindbis) 바이러스, 남방 코끼리 물범 바이러스, 토나테 (Tonate) 바이러스, 트로카라 (Trocara) 바이러스, 우나 (Una) 바이러스, 베네수엘라 말뇌염 바이러스 (VEEV), 서부 말뇌염 바이러스 (WEEV), 화타로아 (Whataroa) 바이러스, 웨스트 나일 (West Nile) 바이러스, 뎅기 바이러스, 진드기-매개 뇌염 바이러스 및 황열 바이러스가 포함된다.
말라리아는 인간 또는 기타 동물 (예를 들어, 마우스) 이 앓고 있는 질환이다. 말라리아의 예에는, 비제한적으로, 열대열 말라리아 원충 (P. falciparum), 사일열 말라리아 원충 (P. malariae), 난형 말라리아 원충 (P. ovale), 삼일열 말라리아 원충 (P. vivax), 원숭이열 말라리아 원충 (P. knowlesi), 쥐열 말라리아 원충 (P. berghei), 카바우디 말라리아 원충 (P. chabaudi) 및 요엘리 말라리아 원충 (P. yoelii) 을 포함하는 말라리아 원충 (Plasmodium (P.)) 종에 의해 야기되는 질환이 포함된다.
본원에 사용된 바, 용어 "말라리아 항원" 은 임의의 항원 또는 이의 단편을 지칭한다. 용어 항원 또는 이의 단편은, 면역 체계에 의해 인지될 수 있고/있거나 세포-매개 면역 반응을 자극하고/하거나 항체의 발생을 자극하는 임의의 펩티드계 서열을 의미한다.
[Scand. J. Immunol. 56, 327-343, 2002] 에 따라, 전반적인 기생충 생활사를 고려하면, 본질적으로 말라리아 백신을 위한 6 가지 표적이 존재한다: (1) 포자소체; (2) 간 단계; (3) 분열소체; (4) 감염된 RBC; (5) 기생충 독소; (6) 성적 단계.
표에는 확인된 각 단계의 주요 후보 항원이 요약되어 있다.
Figure pat00001
본 발명에 있어서, 상기 열거된 하나 이상의 항원은, 이들이 입자로 형성되는 한, 사용될 수 있다. 예를 들어, 포자소체 단백질 및 이의 단편은 항원으로 사용될 수 있다. 포자소체 단백질의 예에는, 비제한적으로, 하기 기재된 아미노산 서열 (SEQ ID No.56) 로 이루어진 열대열 말라리아 원충 포자소체 단백질이 포함된다:
Mmrklailsvssflfvealfqeyqcygsssntrvlnelnydnagtnlynelemnyygkqenwyslkknsrslgenddgnnnngdngregkdedkrdgnnedneklrkpkhkklkqpgdgnpdpnanpnvdpnanpnvdpnanpnvdpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnvdpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnknnqgngqghnmpndpnrnvdenanannavknnnneepsdkhieqylkkiknsistewspcsvtcgngiqvrikpgsankpkdeldyendiekkickmekcssvfnvvnssiglimvlsflflntr.
일 구현예에서, 말라리아 항원은 열대열 말라리아 원충 포자소체 단백질 B 세포 항원결정부 (epitope) 이다. 열대열 말라리아 원충 포자소체 단백질 B 세포 항원결정부의 예는, (NPNA)4-30 (즉, 4xNPNA, 5xNPNA, 6xNPNA, 7xNPNA, 8xNPNA, 9xNPNA, 10xNPNA, 11xNPNA, 12xNPNA, 13xNPNA, 14xNPNA, 15xNPNA, 16xNPNA, 17xNPNA, 18xNPNA, 19xNPNA, 20xNPNA, 21xNPNA, 22xNPNA, 23xNPNA, 24xNPNA, 25xNPNA, 26xNPNA, 27xNPNA, 28xNPNA, 29xNPNA 또는 30xNPNA) 을 포함하는 NPNA 의 반복 서열일 수 있다.
일 구현예에서, 말라리아 항원은 (QGPGAP)3-12 를 포함하는 요엘리 말라리아 원충 (Plasmodium yoelii) 포자소체 단백질 B 세포 항원결정부이다.
일 구현예에서, 말라리아 항원은 (ANGAGNQPG)1-12 를 포함하는 삼일열 말라리아 원충 포자소체 단백질 B 세포 항원결정부이다.
일 구현예에서, 말라리아 항원은 (NAAG)4-30 을 포함하는 사일열 말라리아 원충 포자소체 단백질 B 세포 항원결정부이다.
일 구현예에서, 말라리아 항원은 열대열 말라리아 원충 포자소체 단백질 T 세포 항원결정부이다. 열대열 말라리아 원충 포자소체 단백질 T 세포 항원결정부의 예는 EYLNKIQNSLSTEWSPCSVT (SEQ ID No.44) 일 수 있다. (EYLNKIQNSLSTEWSPCSVT)1-6 이 또한 말라리아 항원으로서 사용될 수 있다.
일 구현예에서, 말라리아 항원은 YNRNIVNRLLGDALNGPEEK (SEQ ID No.45) 인, 요엘리 말라리아 원충 (Plasmodium yoelii) 포자소체 단백질 T 세포 항원결정부이다. (YNRNIVNRLLGDALNGPEEK)1-6 이 또한 말라리아 항원으로서 사용될 수 있다.
본 발명은 항원, 항원을 인코딩하는 벡터, 및 항원에 특이적으로 결합하는 항체 (및 압타머 (aptamer) 및 펩티드를 포함하는 항체-유사 분자), 및 말라리아 감염의 예방 또는 치료에서의 이의 용도 (단독으로 또는 조합으로) 를 제공함으로써 상기 요구 중 하나 이상을 다룬다. 본원에 사용된 바, 용어 "항체" 는 항원결정부 또는 항원 결정인자와 결합가능한 분자를 지칭한다. 상기 용어는 단쇄 항체를 포함하는, 전체 항체 및 이의 항원-결합 단편을 포함하는 것으로 의도된다. 상기와 같은 항체에는, 인간 항원 결합 항체 단편이 포함되고, 이에는, 비제한적으로, Fab, Fab' 및 F(ab')2, Fd, 단쇄 Fvs (scFv), 단쇄 항체, 디술피드-연결된 Fvs (sdFv) 및 VL 또는 VH 도메인을 포함하는 단편이 포함된다. 항체는 조류 및 포유류를 포함하는 임의의 동물 유래일 수 있다. 바람직하게는, 항체는 포유류, 예를 들어 인간, 쥐, 토끼, 염소, 기니어 피그, 낙타, 말 등, 또는 기타 적합한 동물, 예를 들어 닭이다. 본원에 사용된 바, "인간" 항체에는, 인간 면역글로불린의 아미노산 서열을 갖는 항체가 포함되고, 예를 들어 미국 특허 번호 5,939,598 에 기재된 바와 같이, 내인성 면역글로불린을 발현하지 않는, 인간 면역글로불린 라이브러리에서 또는 하나 이상의 인간 면역글로불린을 위한 유전자 이식된 동물에서 단리된 항체가 포함되며, 상기 특허는 그 전문이 본원에 참조로서 인용된다.
본 발명에 사용되는 항원은 자연 발생 단백질 유래의 개질된 폴리펩티드일 수 있다. 개질된 폴리펩티드는 자연 발생 단백질의 단편일 수 있다. 일 구현예에서, 개질된 폴리펩티드는 자연 발생 단백질 유래의 폴리펩티드와 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 이상의 아미노산 서열 동일성을 갖는다. 일 구현예에서, 상기와 같이 유래된 개질된 폴리펩티드는, 자연 발생 단백질 유래의 폴리펩티드를 기준으로, 최대 10% 의 아미노산이 제거, 치환 및/또는 첨가된 돌연변이이다.
본 발명에 의해 제공되는 입자에서, 폴리펩티드 및 항원은 폴리펩티드에 존재하는 하나 이상의 제 1 부착 부위 및 항원에 존재하는 하나 이상의 제 2 부착 부위를 통해 연결될 수 있다.
본원에 사용된 바, "제 1 부착 부위" 및 "제 2 부착 부위" 는 각각 1 개 초과의 물질이 서로 연결되는 부위를 지칭한다.
일 구현예에서, 폴리펩티드 및 항원은 직접 융합된다. 대안적으로, 1 또는 2 개의 링커가 항원의 N-말단 잔기와 폴리펩티드 사이 및/또는 항원의 C-말단 잔기와 폴리펩티드 사이에 개재될 수 있다.
항원 또는 폴리펩티드는 절단 및 짧은 링커로 대체될 수 있다. 일부 구현예에서, 항원 또는 폴리펩티드는 하나 이상의 펩티드 링커를 포함한다. 통상적으로, 링커는 2 내지 25 개의 아미노산으로 이루어진다. 특정한 경우, 단일 글리세린 잔기와 같이 오로지 1 개의 아미노산으로 이루질 수 있으나, 일반적으로는 2 내지 15 개의 아미노산 길이를 갖는다.
일 구현예에서, 폴리펩티드를 인코딩하는 폴리뉴클레오티드가 항원을 인코딩하는 폴리뉴클레오티드와 유전적으로 융합된 핵산 분자는, 숙주 세포에서 발현되기 때문에, 제 1 부착 부위 및 제 2 부착 부위는 펩티드 결합을 통해 연결된다. 이러한 경우, 폴리펩티드 및 항원은 펩티드 결합을 통해 연결된다. 이러한 구현예에 관련하여, 제 1 부착 부위 및/또는 제 2 부착 부위는 본래의 폴리펩티드 또는 항원으로부터 유전적으로 개질될 수 있다. 예를 들어, 제 1 부착 부위는 폴리펩티드로부터 개질되기 때문에, SG, GS, SGG, GGS 및 SGSG 를 포함하는 링커 펩티드를 통해, 폴리펩티드는 항원과 공액된다.
폴리펩티드가 항원과 화학적으로 공액되는 경우, 제 1 부착 부위 및 제 2 부착 부위는 화합물인 화학적 가교제를 통해 연결될 수 있다.
가교제의 예에는, 비제한적으로, SMPH, Sulfo-MBS, Sulfo-EMCS, Sulfo-GMBS, Sulfo-SIAB, Sulfo-SMPB, Sulfo-SMCC, SVSB, SIA 및 Pierce Chemical Company 사에서 시판되는 기타 가교제가 포함된다.
일 구현예에서, 본 발명에 의해 제공되는 입자는 항원에 연결된 폴리펩티드를 포함하고, 여기서 항원의 N-말단 잔기와 C-말단 잔기 사이의 공간 거리는, 항원 또는 항원 함유 자연 발생 단백질 또는 이로부터 개질된 단백질의 결정에서 측정 시, 30Å 이하이다.
본 발명에 사용되는 항원은 당업자에 의해 고안될 수 있다. 예를 들어, 본 발명에 사용되는 항원은 자연 발생 단백질 또는 이의 단편일 수 있다. 대안적으로, 본 발명에 사용되는 항원은 자연 발생 단백질 또는 이의 단편으로부터 개질된 단백질일 수 있다. 당업자는 항원의 N-말단 잔기와 C-말단 잔기 사이의 공간 거리가, 항원 또는 항원 함유 자연 발생 단백질 또는 이로부터 개질된 단백질의 결정에서 측정 시, 30Å 이하가 되도록 항원을 고안할 수 있다. 예를 들어, 본 발명에 의해 제공된 입자에 사용되는 항원은 PyMOL (예를 들어, PyMOL v0.99: http:/www.pymol.org) 를 비롯한 무료 소프트웨어를 사용하여 고안될 수 있다. 일 구현예에서, 항원의 N-말단 잔기와 C-말단 잔기 사이의 공간 거리는 30Å (옹스트롬) 이하, 20Å 이하, 또는 10Å 이하 (예를 들어, 5 Å 내지 15 Å, 5 Å 내지 12 Å, 5 Å 내지 11 Å, 5 Å 내지 10 Å, 5 Å 내지 8 Å, 8 Å 내지 15 Å, 8 Å 내지 13 Å, 8 Å 내지 12 Å, 8 Å 내지 11 Å, 9 Å 내지 12 Å, 9 Å 내지 11 Å, 9 Å 내지 10 Å 또는 10 Å 내지 11 Å) 이다.
치쿤군야 바이러스 유사 입자 또는 베네수엘라 말뇌염 바이러스 유사 입자
일 구현예에서, 본 발명은 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드 및 하나 이상의 말라리아 항원을 포함하는 치쿤군야 바이러스 유사 입자 또는 베네수엘라 말뇌염 바이러스 유사 입자로서, 상기 치쿤군야 바이러스 구조 폴리펩티드 또는 상기 베네수엘라 말뇌염 바이러스 구조 폴리펩티드는 하나 이상의 제 1 부착 부위를 포함하고, 상기 하나 이상의 말라리아 항원은 하나 이상의 제 2 부착 부위를 포함하며, 상기 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드 및 상기 하나 이상의 항원은 상기 하나 이상의 제 1 및 상기 하나 이상의 제 2 부착 부위를 통해 연결되는 입자를 제공한다.
일 구현예에서, 말라리아 항원의 N-말단 잔기와 C-말단 잔기 사이의 공간 거리는, 말라리아 항원 또는 말라리아 항원 함유 자연 발생 단백질 또는 이로부터 개질된 단백질의 결정에서 측정 시, 30 Å 이하; 25 Å 이하; 20 Å 이하; 15 Å 이하; 14 Å 이하; 13 Å 이하; 12 Å 이하; 11 Å 이하; 10 Å 이하; 9 Å 이하; 또는 8 Å 이하 (예를 들어, 5 Å 내지 15 Å, 5 Å 내지 12 Å, 5 Å 내지 11 Å, 5 Å 내지 10 Å, 5 Å 내지 8 Å, 8 Å 내지 15 Å, 8 Å 내지 13 Å, 8 Å 내지 12 Å, 8 Å 내지 11 Å, 9 Å 내지 12 Å, 9 Å 내지 11 Å, 9 Å 내지 10 Å 또는 10 Å 내지 11 Å) 일 수 있다.
일 구현예에서, 말라리아 항원은 화학적 가교에 의해 또는 유전 공학에 의해 제조된 융합 단백질로서 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드에 연결된다.
본 발명에 사용되는 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드는 치쿤군야 또는 베네수엘라 말뇌염 바이러스 외피 단백질 및/또는 캡시드를 포함할 수 있다.
치쿤군야 바이러스의 예에는, 비제한적으로, 37997 및 LR2006 OPY-1 의 균주가 포함된다.
베네수엘라 말뇌염 바이러스의 예에는, 비제한적으로, TC-83 이 포함된다.
본 발명에 사용되는 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드는 자연 발생 바이러스 구조 폴리펩티드 또는 이의 개질된 폴리펩티드일 수 있다. 개질된 폴리펩티드는 자연 발생 바이러스 구조 폴리펩티드의 단편일 수 있다. 일 구현예에서, 개질된 폴리펩티드는 자연 발생 바이러스 캡시드 및/또는 외피 단백질과 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 이상의 아미노산 서열 동일성을 갖는다. 일 구현예에서, 개질된 폴리펩티드는, 자연 발생 바이러스 캡시드 및/또는 외피 단백질을 기준으로, 최대 10% 의 아미노산이 제거, 치환 및/또는 첨가된 돌연변이이다. 예를 들어, K64A 또는 K64N 돌연변이가 본 발명에 사용된 베네수엘라 말뇌염 바이러스 구조 폴리펩티드의 캡시드 내에 도입될 수 있다.
치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드는 캡시드, E2 및 E1 로 이루어지거나 또는 이를 포함할 수 있다.
치쿤군야 바이러스 구조 폴리펩티드의 예에는, 비제한적으로, 치쿤군야 바이러스 균주 37997 의 캡시드- E2-E1, 및 치쿤군야 바이러스 LR2006 OPY-1 의 캡시드- E2-E1 가 포함된다.
베네수엘라 말뇌염 바이러스 구조 폴리펩티드의 예에는, 비제한적으로, 베네수엘라 말뇌염 바이러스 균주 TC-83 의 캡시드- E2-E1 이 포함된다.
대표적인 치쿤군야 바이러스 구조 폴리펩티드 서열은 Genbank Accession No. ABX40006.1 에서 제공된 것으로, 이는 하기 기재되는 바와 같다 (SEQ ID No.1):
Figure pat00002
.
또 다른 대표적인 치쿤군야 바이러스 구조 폴리펩티드 서열은 Genbank Accession No. ABX40011.1 에서 제공된 것으로, 이는 하기 기재되는 바와 같다 (SEQ ID No.2):
Figure pat00003
.
대표적인 베네수엘라 말뇌염 바이러스 구조 폴리펩티드는 하기 기재되는 바와 같다 (SEQ ID No.3):
Figure pat00004
일 구현예에서, 제 1 부착 부위는 아미노기, 바람직하게는 리신 잔기의 아미노기를 포함한다. 일 구현예에서, 제 2 부착 부위는 술프히드릴기, 바람직하게는, 시스테인의 술프히드릴기를 포함한다.
일 구현예에서, 제 1 부착 부위 또는 제 2 부착 부위를 통한 2 개 초과 물질 (예를 들어, 항원 및 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드) 의 공액은 화학적 가교제를 사용하여 달성된다. 가교제의 예에는, 비제한적으로, SMPH, Sulfo-MBS, Sulfo-EMCS, Sulfo-GMBS, Sulfo-SIAB, Sulfo-SMPB, Sulfo-SMCC, SVSB, SIA 및 Pierce Chemical Company 사에서 시판되는 기타 가교제가 포함된다.
본 발명에 따라, 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드 및 항원을 포함하는 치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자로서, 상기 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드 및 상기 항원이 융합 단백질로서 발현되는 입자가 제공될 수 있다.
일 구현예에서, 항원은 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드의 임의의 부위와 융합될 수 있다. 예를 들어, 항원은 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드의 N- 또는 C- 말단에 직접 또는 간접적으로 연결될 수 있거나, 또는 항원은 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 단백질 내에 삽입될 수 있다.
일 구현예에서, 하나 이상의 항원은 치쿤군야 또는 베네수엘라 말뇌염 바이러스 구조 단백질의 E2 내에 삽입된다. 예를 들어, 치쿤군야 바이러스 구조 단백질에 있어서, 하나 이상의 항원은 SEQ ID No.1 또는 2 의 잔기 519 와 520 사이 (즉, SEQ ID No.1 또는 2 의 519-위치의 G 와 520-위치의 Q 사이); SEQ ID No.1 또는 2 의 잔기 530 과 531 사이 (즉, SEQ ID No.1 또는 2 의 530-위치의 G 와 531-위치의 S 사이); SEQ ID No.1 또는 2 의 잔기 531 과 532 사이 (즉, SEQ ID No.1 또는 2 의 531-위치의 S 와 532-위치의 N 사이); SEQ ID No.1 또는 2 의 잔기 529 와 530 사이 (즉, SEQ ID No.1 또는 2 의 529-위치의 G 와 530-위치의 G 사이); 또는 SEQ ID No.1 또는 2 의 잔기 510 과 511 사이 (즉, SEQ ID No.1 또는 2 의 510-위치의 S 와 511-위치의 G 사이); 또는 SEQ ID No.1 또는 2 의 잔기 511 과 512 사이 (즉, SEQ ID No.1 또는 2 의 511-위치의 G 와 512-위치의 N 사이); 또는 SEQ ID No.1 또는 2 의 잔기 509 와 510 사이 (즉, SEQ ID No.1 또는 2 의 509-위치의 Q 와 510-위치의 S 사이) 에 삽입된다.
예를 들어, 베네수엘라 말뇌염 바이러스 구조 단백질에 있어서, 하나 이상의 항원은 SEQ ID No.3 의 잔기 517 과 518 사이 (즉, SEQ ID No.3 의 517-위치의 G 와 518-위치의 S 사이); SEQ ID No.3 의 잔기 518 과 519 사이 (즉, SEQ ID No.3 의 518-위치의 S 와 519-위치의 S 사이); SEQ ID No.3 의 잔기 519 과 520 사이 (즉, SEQ ID No.3 의 519-위치의 S 와 520-위치의 V 사이); SEQ ID No.3 의 잔기 515 와 516 사이 (즉, SEQ ID No.3 의 515-위치의 L 과 516-위치의 S 사이); SEQ ID No.3 의 잔기 516 과 517 사이 (즉, SEQ ID No.3 의 516-위치의 S 와 517-위치의 G 사이); SEQ ID No.3 의 잔기 536 과 537 사이 (즉, SEQ ID No.3 의 536-위치의 C 와 537-위치의 G 사이); SEQ ID No.3 의 잔기 537 과 538 사이 (즉, SEQ ID No.3 의 537-위치의 G 와 538-위치의 G 사이); SEQ ID No.3 의 잔기 538 과 539 사이 (즉, SEQ ID No.3 의 538-위치의 G 와 539-위치의 T 사이) 에 삽입된다.
융합 단백질은 업계의 통상의 기법을 사용하여 발현시킬 수 있다. 각종 발현 시스템이 융합 단백질의 발현에 사용될 수 있다. 예를 들어, 융합 단백질은 293 세포, Sf9 세포 또는 대장균 (E.coli) 에서 발현될 수 있다.
치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 유래의 폴리펩티드는 자연 발생 바이러스 폴리펩티드 또는 이의 개질된 폴리펩티드일 수 있다. 또한, 말라리아 항원 유래의 폴리펩티드는 자연 발생 폴리펩티드 또는 자연 발생 폴리펩티드의 개질된 폴리펩티드 또는 자연 발생 폴리펩티드 또는 개질된 펩티드의 단편일 수 있다. 개질된 폴리펩티드는 자연 발생 바이러스 구조 폴리펩티드의 단편일 수 있다.
일 구현예에서, 말라리아 항원 유래의 개질된 폴리펩티드는 자연 발생 폴리펩티드와 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 이상의 아미노산 서열 동일성을 갖는다. 일 구현예에서, 말라리아 항원 유래의 개질된 폴리펩티드는, 말라리아 항원 유래의 자연 발생 폴리펩티드를 기준으로, 최대 10% 의 아미노산이 제거, 치환 및/또는 첨가된 돌연변이이다.
바이러스 유래의 폴리펩티드가 항원 유래의 폴리펩티드와 공액되는 경우, SG, GS, SGG, GGS, SGSG 및 TRGGS 를 포함하는 링커 펩티드가 사용될 수 있다. 바이러스 유래의 폴리펩티드 (하기에 "PVF" 로서 지칭됨) 와 항원 유래의 폴리펩티드 (하기에 "PFA" 로서 지칭됨) 의 공액의 예에는, 비제한적으로 하기가 포함된다: PFV-SG-PFA-GS-PFV; PFV-SG-PFA-GGS-PFV; PFV-SSG-PFA-GS-PFV; PFV-SGG-PFA-GGS-PFV; PFV-SGSG-PFA-GS-PFV; 및 PFA-SGG-PFA-TRGGS-PFV.
일 구현예에서, 본 발명은 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 유래의 폴리펩티드 및 말라리아 항원 유래의 폴리펩티드의 융합 단백질을 포함하는 바이러스 유사 입자로서, 상기 바이러스 유사 입자는, SEQ ID NO. 28, 31, 34, 37, 39, 41 또는 43 으로 표시되는 아미노산 서열에 해당하는 핵산 분자를 포함하는 발현 벡터를, 포유류 세포 (예를 들어, 293F 세포) 내에 트랜스펙션함으로써 제조되는 입자를 제공한다. 이러한 구현예에 있어서, 개질된 융합 단백질이 또한 본 발명에 의해 제공되는 바이러스 유사 입자에 사용될 수 있고, 이는 SEQ ID NO. 28, 31, 34, 37, 39, 41 또는 43 과 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 이상의 아미노산 서열 동일성을 갖는 아미노산 서열에 해당하는 핵산 분자를 포함하는 발현 벡터를, 포유류 세포 (예를 들어, 293F 세포) 내에 트랜스펙션함으로써 제조될 수 있다.
일 구현예에서, 본 발명은,
1 종 이상의, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 캡시드;
1 종 이상의, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 E1; 및
1 종 이상의, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 E2
를 포함하거나 이로 이루어지는 바이러스 유사 입자로서,
말라리아 항원이 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 E2 내에 삽입되는 입자를 제공한다. 예를 들어, 본 발명은,
240 종의, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 캡시드;
240 종의, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 E1; 및
240 종의, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 E2
를 포함하거나 이로 이루어지는 바이러스 유사 입자로서,
말라리아 항원이 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 각각의 E2 내에 삽입되는 입자를 제공한다.
이러한 구현예에서, 항원이 그 안에 삽입되는 E2 는 SEQ ID No.50 으로 표시되는 아미노산 서열로 이루어질 수 있고; E1 은 SEQ ID No.51 로 표시되는 아미노산 서열로 이루어질 수 있고; 캡시드는 SEQ ID No.52 로 표시되는 아미노산 서열로 이루어질 수 있거나; 또는
항원이 그 안에 삽입되는 E2 는 SEQ ID NO.53 으로 표시되는 아미노산 서열로 이루어질 수 있고; E1 은 SEQ ID NO.54 로 표시되는 아미노산 서열로 이루어질 수 있고; 캡시드는 SEQ ID NO.55 로 표시되는 아미노산 서열로 이루어질 수 있다.
나아가, 이러한 구현예에 있어서, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 개질된 캡시드, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 개질된 E1 및 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 개질된 E2 가 바이러스 유사 입자에 사용될 수 있다. 예를 들어, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 개질된 캡시드는 SEQ ID No.52 또는 SEQ ID No.55 로 표시되는 아미노산 서열과 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 이상의 아미노산 서열 동일성을 가질 수 있고; 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 개질된 E1 은 SEQ ID NO.51 또는 SEQ ID No.54 로 표시되는 아미노산 서열과 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 이상의 아미노산 서열 동일성을 가질 수 있고/있거나; 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 개질된 E2 는 SEQ ID NO.50 또는 SEQ ID No.53 으로 표시되는 아미노산 서열과 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 이상의 아미노산 서열 동일성을 가질 수 있다.
또한, 개질된 캡시드, E1 또는 E2 는, SEQ ID No.52 또는 SEQ ID No.55 로 표시되는 아미노산 서열로 이루어진 캡시드; SEQ ID NO.51 또는 SEQ ID No.54 로 표시되는 아미노산 서열로 이루어진 E1; 및/또는 SEQ ID NO.50 또는 SEQ ID No.53 으로 표시되는 아미노산 서열로 이루어진 E2 를 기준으로, 최대 10% 의 아미노산이 제거, 치환 및/또는 첨가된 돌연변이일 수 있다.
(2) 뉴클레오티드, 벡터, 숙주 세포
제 2 양태에서, 본 발명은 본 발명의 제 1 양태에서 제공된 입자의 발현을 위하여 고안된 핵산 분자를 제공한다.
일 구현예에서, 본 발명은 상기 기재된 바와 같은 치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자를 인코팅하는 뉴클레오티드 서열을 포함하는 핵산 분자를 제공한다.
치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자를 인코딩하는 뉴클레오티드 서열의 예에는, 비제한적으로, 치쿤군야 바이러스 균주 37997 의 외피를 인코딩하는 뉴클레오티드 서열, 치쿤군야 바이러스 균주 37997 의 캡시드-외피를 인코딩하는 뉴클레오티드 서열, 치쿤군야 바이러스 균주 LR2006 OPY-1 의 외피를 인코딩하는 뉴클레오티드 서열, 치쿤군야 바이러스 LR2006 OPY-1 의 캡시드-외피를 인코딩하는 뉴클레오티드 서열, 베네수엘라 말뇌염 바이러스 균주 TC-83 의 외피를 인코딩하는 뉴클레오티드 서열 및 베네수엘라 말뇌염 바이러스 TC-83 의 캡시드-외피를 인코딩하는 뉴클레오티드 서열이 포함된다.
치쿤군야 바이러스에 있어서, 외피를 인코딩하는 대표적인 뉴클레오티드 서열은 하기 기재되는 바와 같다 (SEQ ID No.4):
Figure pat00005
.
치쿤군야 바이러스에 있어서, 외피를 인코딩하는 또 다른 대표적인 뉴클레오티드 서열은 하기 기재되는 바와 같다 (SEQ ID No.5):
Figure pat00006
.
치쿤군야 바이러스에 있어서, 캡시드-외피를 인코딩하는 대표적인 뉴클레오티드 서열은 하기 기재되는 바와 같다 (SEQ ID No.6):
Figure pat00007
Figure pat00008
치쿤군야 바이러스에 있어서, 캡시드-외피를 인코딩하는 또 다른 대표적인 뉴클레오티드 서열은 하기 기재되는 바와 같다 (SEQ ID No.7):
Figure pat00009
Figure pat00010
일 구현예에서, 본 발명은 상기 기재된 바와 같은 핵산 분자를 포함하는 벡터로서, 핵산 분자에 작동가능하게 연결된 발현 조절 서열을 임의로 포함하는 벡터를 제공한다.
발현 조절 서열의 예에는, 비제한적으로, 프로모터 (promoter), 예컨대 CMV 프로모터, 람다 파지 PL 프로모터, 대장균 (E. coli) lac, phoA 및 tac 프로모터, SV40 초기 및 후기 프로모터, 및 레트로바이러스 LTR 의 프로모터가 포함된다.
이러한 구현예에서, 상기 기재된 바와 같은 핵산 분자에 작동가능하게 연결된 발현 조절 서열을 포함하는 벡터는, 본 발명의 제 1 양태에 의해 제공된 입자의 제조를 위한 발현 벡터로서 사용될 수 있다.
상기 발현 벡터는 WO/2012/006180 을 기반으로 당업자에 의해 제조될 수 있고, 상기 특허 문헌은 그 전문이 본원에 참조로서 인용된다.
치쿤군야 바이러스 (CHIKV) 유래의 폴리펩티드 및 항원의 폴리펩티드의 융합 단백질을 포함하는 바이러스 유사 입자를 발현시키기 위해 사용될 수 있는 벡터의 예에는, CHIKV VLP 폴리뉴클레오티드 (SEQ ID No. 13; SEQ ID No.14 로 표시되는 해당 아미노산 서열) 를 함유하는 VLP_CHI 512 벡터 (SEQ ID No.8); 및 CHIKV VLP 폴리뉴클레오티드 (SEQ ID No. 15; SEQ ID No.16 으로 표시되는 해당 아미노산 서열) 를 함유하는 VLP_CHI 532 벡터 (SEQ ID No. 9) 로 제시되는 벡터가 포함된다.
상기 발현 벡터는 US2012/0003266 을 기반으로 당업자에 의해 제조될 수 있고, 상기 특허 문헌은 그 전문이 본원에 참조로서 인용된다.
베네수엘라 말뇌염 바이러스 (VEEV) 유래의 폴리펩티드 및 항원의 폴리펩티드의 융합 단백질을 포함하는 바이러스 유사 입자를 발현시키기 위해 사용될 수 있는 벡터의 예에는, VEEV VLP 폴리뉴클레오티드 (SEQ ID No. 17; SEQ ID No.18 로 표시되는 해당 아미노산 서열) 를 함유하는 VLP_VEEV VLP 518 벡터 (SEQ ID No.10); VEEV VLP 폴리뉴클레오티드 (SEQ ID No. 19; SEQ ID No.20 으로 표시되는 해당 아미노산 서열) 를 함유하는 VLP_VEEV VLP 519 벡터 (SEQ ID No.11); 및 VEEV VLP 폴리뉴클레오티드 (SEQ ID No. 21; SEQ ID No.22 로 표시되는 해당 아미노산 서열) 를 함유하는 VLP_VEEV VLP 538 벡터 (SEQ ID No. 12) 로 제시되는 벡터가 포함된다.
일 구현예에서, 본 발명은 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 유래의 폴리펩티드 및 말라리아 항원 유래의 폴리펩티드의 융합 단백질을 포함하는 바이러스 유사 입자의 발현을 위해 고안된 핵산 분자로서, SEQ ID No.26-27, 29-30, 32-33, 35-36, 38, 40 또는 42 로 표시되는 뉴클레오티드 서열로 이루어진 핵산 분자를 제공한다.
일 구현예에서, 본 발명은 SEQ ID No.26-27, 29-30, 32-33 또는 35-36, 38, 40 또는 42 중 어느 하나로 표시되는 뉴클레오티드 서열을 갖는 핵산 분자로부터 개질된 핵산 분자를 제공한다. 개질된 핵산 분자는 SEQ ID No.26-27, 29-30, 32-33, 35-36, 38, 40 또는 42 중 어느 하나로 표시되는 뉴클레오티드 서열을 갖는 핵산 분자와 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 이상의 뉴클레오티드 서열 동일성을 가질 수 있다. 또한, 개질된 핵산 분자는, SEQ ID No.26-27, 29-30, 32-33, 35-36, 38, 40 또는 42 중 어느 하나로 표시되는 뉴클레오티드 서열을 갖는 핵산 분자를 기준으로, 최대 10% 의 아미노산이 제거, 치환 및/또는 첨가된 돌연변이일 수 있다.
(3) 조성물 또는 백신
제 3 양태에서, 본 발명은 본 발명의 제 1 양태에서 제공된 입자 및/또는 본 발명의 제 2 양태에서 제공된 핵산 분자를 포함하는 조성물 또는 백신을 제공한다.
일 구현예에서, 본 발명은 상기 기재된 바와 같은 알파바이러스 또는 플라비바이러스 바이러스 유사 입자 (예를 들어, 치쿤군야 바이러스 유사 입자 또는 베네수엘라 말뇌염 바이러스 유사 입자) 또는 상기 기재된 바와 같은 핵산 분자를 포함하는 조성물 또는 백신을 제공한다. 알파바이러스 또는 플라비바이러스 바이러스 유사 입자의 함량 및 핵산 분자의 함량은 0.00001-1 w/w% 일 수 있다.
본 발명의 제 1 양태에서 제공된 입자 (예를 들어, CHIKV VLP 또는 VEEV VLP) 의 투여량은 1-500㎍/day 이다.
본 발명의 제 3 양태에 의해 제공되는 하나의 조성물 또는 하나의 백신에 하나 이상의 말라리아 항원이 사용될 수 있다.
조성물 또는 백신은 약학적으로 허용가능한 담체 및/또는 보조제를 추가로 포함할 수 있다. 보조제의 예에는, 비제한적으로, 알루미늄 염, 수산화나트륨, 프로인드 완전 보조제 (Freund's complete adjuvant), 프로인드 불완전 보조제 (Freund's incomplete adjuvant) 및 Ribi 용액 (Sigma Adjuvant system, Sigma-Aldrich) 이 포함된다. 본 발명의 제 3 양태에서 제공된 조성물 또는 백신은 완충제, 예컨대 2염기성 인산나트륨 수화물, 인산이수소나트륨 및 염화나트륨; 및 보존제, 예컨대 티메로살을 함유할 수 있다. 일 구현예에서, 조성물 또는 백신은 0.001-1 w/w% 의 본 발명의 제 1 양태에서 제공된 입자 (예를 들어, CHIKV VLP 또는 VEEV VLP), 1-10w/w% 의 완충제, 0.01-1w/w% 의 보조제 및 0.00001-0.001w/w% 의 보존제를 함유하는 수용액이다.
당업자는 통상의 기법을 사용하여 약학적 조성물 및 백신을 제조할 수 있다. 예를 들어, 본 발명의 제 1 양태에서 제공된 입자를 생리학적 pH (예를 들어, pH 5-9, pH 7) 를 갖는 완충액과 혼합하여, 본 발명의 제 3 양태에서 제공된 약학적 조성물 및 백신을 제조한다.
본 발명의 약학적 조성물은, 본 발명의 목적에 반하지 않는 한, 단일 활성 성분 또는 둘 이상의 활성 성분의 조합을 함유할 수 있다. 예를 들어, 케모카인을 포함하는 사이토카인, 사이토카인의 항체, 예컨대 항 TNF 항체 (예를 들어, 인플릭시맙 (infliximab), 아달리무맙 (adalimumab)), 항-VEGF 항체 (예를 들어, 베바시주맙 (bevacizumab) 및 라니비주맙 (ranibizumab)), 사이토카인 수용체 길항제, 예컨대 항 HER2 항체 (예를 들어, 트라스투주맙 (trastuzumab)), 항 EGF 수용체 항체 (예를 들어, 세툭시맙 (cetuximab)), 항 VEGF 압타머 (예를 들어, 페갑타닙 (pegaptanib)) 및 면역조절제, 예컨대 시클로스포린 (cyclosporine),　타크롤리무스 (tacrolimus), 우베니멕스 (ubenimex) 가 조합 치료에 사용될 수 있다.
복수의 활성 성분의 조합에서, 이의 각각의 함량은 이의 치료적 효과 및 안정성을 고려하여 적합하게 증가 또는 감소될 수 있다.
본원에 사용된 바, 용어 "조합" 은 둘 이상의 활성 성분이 단일 단위 또는 투여량 형태로 동시에 환자에게 투여되거나, 또는 두 개의 활성 성분이 별개의 단위로서 동시에 또는 특정한 시간 제한 없이 순차적으로 투여되는 것을 의미하고, 여기서 상기와 같은 투여는 두 개의 성분의 치료적 유효 수준을, 바람직하게는 동시에 신체에 제공한다.
일 구현예에서, 조성물은 DNA 백신을 포함하는 백신 조성물이다. 일 구현예에서, 본 발명에 의해 제공되는 DNA 백신은 CpG 함유 올리고뉴클레오티드를 포함한다.
본 발명의 제 3 양태에서 제공된 조성물 또는 백신은 1 회 이상 투여될 수 있다. 본 발명의 제 3 양태에서 제공된 조성물 또는 백신이 1 회 초과로 투여되는 경우, 본 발명의 제 1 양태에서 제공된 상이한 입자들 (예를 들어, CHIKV VLP 또는 VEEV VLP) 이 각각의 투여에 사용될 수 있다. 일 구현예에서, 본 발명의 제 1 양태에서 제공된 CHIKV VLP 를 사용하는 면역화 및 본 발명의 제 1 양태에서 제공된 VEEV VLP 를 사용하는 면역화의 조합이 이용된다. 예를 들어, 본 발명의 제 1 양태에서 제공된 CHIKV VLP 가 1 차 면역화에 사용되고, 본 발명의 제 1 양태에서 제공된 VEEV VLP 가 2 차 면역화에 사용될 수 있거나, 또는 본 발명의 제 1 양태에서 제공된 VEEV VLP 가 1 차 면역화에 사용되고, 본 발명의 제 1 양태에서 제공된 CHIKV VLP 가 2 차 면역화에 사용될 수 있다.
당업자는 본 발명의 제 3 양태에서 제공된 조성물 또는 백신을 사용하는 면역화의 시기를 결정할 수 있다. 예를 들어, 2 차 면역화는 1 차 면역화 후 1, 2, 3, 4, 5, 6, 7, 8, 9 또는 10 주차에 수행된다.
일 구현예에서, 본 발명은,
(a) 본 발명의 제 1 양태에서 제공된 입자를 포함하는 백신 조성물; 및
(b) 본 발명의 제 1 양태에서 제공된 입자를 포함하는 또 다른 백신 조성물
을 포함하는 키트로서,
(a) 에 함유된 입자는 (b) 에 함유된 입자와 상이한 바이러스 유사 입자인 키트를 제공한다. 이러한 구현예에서, (a) 에 함유된 입자는 치쿤군야 바이러스 유사 입자일 수 있고, (b) 에 함유된 입자는 베네수엘라 말뇌염 바이러스 유사 입자일 수 있다.
일 구현예에서, 본 발명은,
(a) 본 발명의 제 1 양태에서 제공된 입자를 포함하는 백신 조성물;
(b) 본 발명의 제 1 양태에서 제공된 입자를 포함하는 또 다른 백신 조성물;
(c) 각각 본 발명의 제 1 양태에서 제공된 입자를 포함하는 하나 이상의 백신 조성물
을 포함하는 키트로서,
(a) 는 면역화의 프라이밍에 사용되고, (b) 및 (c) 는 면역화의 부스팅에 사용되며; (a) 에 함유된 입자는 (b) 에 함유된 입자와 상이한 바이러스 유사 입자이고; (c) 에 함유된 입자는 (a) 및 (b) 에 함유된 입자와 상이하거나, 또는 (a) 또는 (b) 에 함유된 입자와 동일한 키트를 제공한다.
상기 기재된 키트에 함유된 각각의 백신 조성물은 동시에, 개별적으로 또는 순차적으로 투여될 수 있다.
본 발명의 제 1 양태에서 제공된 알파바이러스 또는 플라비바이러스 바이러스 유사 입자 (예를 들어, 치쿤군야 바이러스 또는 베네수엘라 말뇌염 바이러스) 또는 본 발명의 제 2 양태에 의해 제공된 핵산 분자가, 본 발명의 제 3 양태에서 제공된 조성물 및 백신에 사용될 수 있다.
예를 들어,
1 종 이상 (예를 들어, 240 종) 의, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 캡시드;
1 종 이상 (예를 들어, 240 종) 의, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 E1; 및
1 종 이상 (예를 들어, 240 종) 의, 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 E2
를 포함하거나 이로 이루어지는 치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자로서, 말라리아 항원이 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 의 E2 내에 삽입되는 입자가, 본 발명의 제 3 양태에서 제공된 조성물 또는 백신의 제조에 사용될 수 있다. 항원이 그 안에 삽입되는 E2 는 SEQ ID No.50 으로 표시되는 아미노산 서열로 이루어질 수 있고; E1 은 SEQ ID No.51 로 표시되는 아미노산 서열로 이루어질 수 있고; 캡시드는 SEQ ID No.52 로 표시되는 아미노산 서열로 이루어질 수 있거나; 또는
항원이 그 안에 삽입되는 E2 는 SEQ ID NO.53 으로 표시되는 아미노산 서열로 이루어질 수 있고; E1 은 SEQ ID NO.54 로 표시되는 아미노산 서열로 이루어질 수 있고; 캡시드는 SEQ ID NO.55 로 표시되는 아미노산 서열로 이루어질 수 있다.
본 발명의 제 3 양태에서 제공된 조성물 또는 백신은 포유류 (예를 들어, 인간) 에 근육내로 (i.m.), 피부내로 (i.c.), 피하로 (s.c.), 피내로 (i.d.) 또는 복강내로 (i.p.) 투여될 수 있다.
본 발명의 제 3 양태에서 제공된 조성물 또는 백신은 말라리아의 치료 또는 예방에 사용될 수 있다.
따라서, 말라리아의 치료 또는 예방을 위한 약학적 조성물 또는 백신의 제조를 위한, 본 발명의 제 1 양태에서 제공된 알파바이러스 또는 플라비바이러스 (예를 들어, 치쿤군야 바이러스 또는 베네수엘라 말뇌염 바이러스) 바이러스 유사 입자 또는 본 발명의 제 2 양태에 의해 제공된 핵산 분자의 용도가 또한 본 발명에 의해 제공된다.
(4) 항체 제조 방법, 면역조절 방법, 말라리아 치료 방법, 포유류에서의 말라리아 항원에 대한 면역 반응 유도 및/또는 증진 방법, 수동 면역 방법, 대식세포 상에의 항원 제시 방법, 및 입자 제조 방법
제 4 양태에서, 본 발명은 본 발명의 제 1 양태에서 제공된 입자 및/또는 본 발명의 제 2 양태에서 제공된 핵산 분자를 포유류에 접촉시키는 것을 포함하는, 항체 제조 방법을 제공한다.
본 발명의 제 4 양태에서 제조된 항체는 통상의 기법을 사용하여 인간화 (humanized) 될 수 있다. 따라서, 일 구현예에서, 본 발명의 제 4 양태에서 제공된 방법은 비(非)인간 포유류용 제조 항체를 인간화시키는 단계를 추가로 포함한다.
본 발명의 제 1 양태에서 제공된 입자 및/또는 본 발명의 제 2 양태에서 제공된 핵산 분자는, 환자에게, 발병 기관에 또는 전신적으로 직접 투여되거나, 또는 환자 유래 세포 또는 인간 세포주에 체외로 적용되고 후속으로 환자에 투여되거나, 또는 생체외에서 환자 유래 면역 세포, 예컨대 B-세포 및 T-세포로부터 부분모집단을 선택하고 이어서 환자에게 재투여되는데 사용될 수 있다.
본 발명에 따라, 바이러스 유사 입자가 면역 치료에 적용될 수 있다.
제 5 양태에서, 본 발명은 본 발명의 제 3 양태에서 제공된 조성물을 포유류에게 투여하는 것을 포함하는, 포유류에서의 면역조절 방법, 말라리아 치료 방법, 말라리아 항원에 대한 면역 반응 유도 및/또는 증진 방법을 제공한다.
제 6 양태에서, 본 발명은 본 발명의 제 4 양태에서 제공된 항체를 포유류에게 투여하는 것을 포함하는, 말라리아-유발 병원체에 대한 수동 면역 방법을 제공한다.
제 7 양태에서, 본 발명은 본 발명의 제 1 양태에서 제공된 입자 및/또는 본 발명의 제 2 양태에서 제공된 핵산 분자를 포유류에 접촉시키는 것을 포함하는, 대식세포 상에의 항원 제시 방법을 제공한다.
제 8 양태에서, 본 발명은 본 발명의 제 1 양태에서 제공된 입자의 제조 방법으로서, 상기 입자의 발현을 위해 고안된 벡터를 제조하고; 상기 벡터로 트랜스펙션된 세포를 배양하여 상기 입자를 발현시키고; 상기 입자를 회수하는 것을 포함하는 방법을 제공한다.
포유류의 예에는, 비제한적으로, 인간이 포함된다.
일 구현예에서, 본 발명은 상기 기재된 바와 같은 치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자 및/또는 상기 기재된 바와 같은 핵산 분자를 포유류에 접촉시키는 것을 포함하는, 말라리아 항원에 대한 항체 제조 방법을 제공한다. 제조된 항체는 치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자 내에 포함된 말라리아 항원 또는 핵산 분자로 인코딩된 말라리아 항원에 특이적으로 결합할 수 있는 항체일 수 있다. 본 발명에 의해 제공되는 항체 제조 방법은 말라리아 항원에 대한 단일클론 또는 다중클론 항체의 제조에 유용할 수 있다.
일 구현예에서, 본 발명에 따른 항체 제조 방법에 의해 수득된 말라리아 항원에 대한 항체가 수동 면역에 사용된다. 수동 면역 방법은 수득된 항체를 포유류에게 투여하는 것을 포함할 수 있다.
일 바람직한 구현예에서, 본 발명에 의해 제공되는 면역조절은 포유류에서 말라리아 항원에 대한 면역 반응을 유도 및/또는 증진시킨다. 따라서, 일 구현예에서, 본 발명은 상기 기재된 바와 같은 조성물의 유효량을 포유류에게 투여하는 것을 포함하는, 포유류에서의 말라리아 항원에 대한 면역 반응 유도 및/또는 증진 방법을 제공한다.
치쿤군야 또는 베네수엘라 말뇌염의 통상의 대분자와 함께 치쿤군야 또는 베네수엘라 말뇌염에 감염된 환자의 증상을 고려할 때, 이러한 VLP 는 표적 대식세포 및 이의 조성물, 예컨대 사이토카인 및 면역조절 화합물에 효과적으로 및 효율적으로 작용할 수 있다.
일 양태에서, 본 발명은 상기 기재된 바와 같은 치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자 및/또는 상기 기재된 바와 같은 핵산 분자를 포유류에게 투여하는 것을 포함하는, 대식세포 상에의 항원 제시 방법을 제공한다. 본 발명에 의해 제공되는 치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자는 표적 대식세포로서 우수하다. 일 구현예에서, 본 발명에 의해 제공되는 치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자는, 치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자에 포함된 하나 이상의 항원의, 대식세포로의 일종의 전달 시스템이다.
일 구현예에서, 본 발명은 본 발명의 제 1 양태에서 제공된 치쿤군야 또는 베네수엘라 말뇌염 바이러스 유사 입자의 제조 방법으로서, 상기 입자의 발현을 위해 고안된 벡터를 제조하고; 상기 벡터로 트랜스펙션된 세포를 배양하여 상기 입자를 발현시키고; 상기 입자를 회수하는 것을 포함하는 방법을 제공한다. 이러한 구현예에서, 트랜스펙션은 통상의 방법을 사용하여 수행될 수 있다. 트랜스펙션에 사용되는 세포는 293 세포일 수 있다. VLP 의 회수는, 세포가 벡터로 트랜스펙션된 후 조정 배지 (conditioned medium) 를 수집하는 것을 포함할 수 있고, 초원심분리를 사용하여 조정 배지로부터 VLP 를 정제하는 것을 추가로 포함할 수 있다.
본 발명을 하기 실시예를 참조로 상세하게 설명할 것이나, 이는 본 발명의 범위를 한정하고자 하는 것이 아니다.
실시예
실시예 1: 바이러스 구조 폴리펩티드 및 말라리아 항원의 단편을 포함하는 치쿤군야 바이러스 (CHIKV) 유사 입자의 제조
하기 말라리아 CSP1 단백질의 폴리뉴클레오티드를 사용하였다. N 말단 링커는 SGG 이고, C 말단 링커는 GGS 였다.
VLP74 (NPNA 아미노산 서열의 6 회 반복)
Sggnpnanpnanpnanpnanpnanpnaggs (SEQ ID No.46)
(Tccggaggaaacccgaatgccaatcccaacgcgaaccccaatgctaacccaaatgccaacccaaacgccaaccccaacgctggtggatcc) (SEQ ID No.47)
VLP78 (NPNA 아미노산 서열의 25 회 반복)
Sggnpnanpnanpnanpnanpnanpnvdpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnanpnaggs (SEQ ID No.48)
(tccggaggaaacccgaatgccaatcccaacgcgaaccccaacgctaaccccaacgccaatccgaatgcaaacccgaacgttgacccaaacgccaacccgaatgccaatcccaacgcgaaccccaatgctaacccaaatgccaacccaaacgccaaccccaacgctaatccaaacgccaaccctaacgccaatcccaacgcgaatcctaacgctaatcccaacgcaaatcccaatgctaatccgaacgcgaaccctaatgcaaaccccaacgccaacccgaacgctaacccgaacgctaatcccaacgccggtggatcc) (SEQ ID No.49)
각각의 폴리뉴클레오티드를 SEQ ID No.15 또는 16 (SEQ ID No.1 또는 2) 의 531-위치의 Ser 및 532-위치의 Asn 을 인코딩하는 코돈 사이에 삽입하여, 치쿤군야 바이러스 유사 입자의 발현을 위한 플라스미드 (이하 CHIKV-VLP74 또는 78 로서 지칭됨) 를 구축하였고, 여기서 개질된 VLP74 또는 78-유래 펩티드는 치쿤군야 바이러스 구조 폴리펩티드의 E2 내에 삽입되었다.
PEI (GE Healthcare) 또는 GeneX (ATCC) 를 사용하여 293F 세포 (Lifetechnology) 를 플라스미드로 트랜스펙션하였다. 트랜스펙션 후 4 일차에, 조정 배지를 수집하고, 3000rpm 에서 15 분 동안 원심분리하여, 이를 세포로부터 분리시켰다. 0.45 ㎛ 필터를 사용하여 상청액을 여과하여, 바이러스 유사 입자를 수득하였다. 바이러스 유사 입자를 TFF 컬럼을 사용하여 농축시키고, QXL 컬럼 (GE Healthcare) 을 사용하여 정제하여, 정제된 바이러스 유사 입자를 수득하였다. 동물이 바이러스 유사 입자로 면역화되는 경우, 정제된 바이러스 유사 입자를 스핀 컬럼 (분자량-차단: 100kDa) 을 사용하여 추가로 농축시켜, 면역화를 위한 바이러스 유사 입자를 제조하였다.
CHIKV (ATCC: VR-1241AF) 특이적 항체 및 VLP74 또는 78 특이적 항체를 사용하여 웨스턴 블롯 (Western Blot) 에 의해, 치쿤군야 바이러스 구조 폴리펩티드와 공액된 VLP74 또는 78 을 포함하는 VLP 의 발현을 확인하였다.
실시예 2: 바이러스 구조 폴리펩티드 및 말라리아 항원의 단편을 포함하는 베네수엘라 말뇌염 바이러스 (VEEV) 유사 입자의 제조
실시예　1 에서 사용된 바와 동일한 말라리아 CSP1 단백질의 폴리뉴클레오티드 (VLP74 및 VLP78) 를 사용하였다. N 말단 링커는 SGG 이고, C 말단 링커는 GGS 였다.
각각의 폴리뉴클레오티드를 SEQ ID No.19 또는 20 (SEQ ID No.3) 의 518-위치의 Ser 및 519-위치의 Ser 을 인코딩하는 코돈 사이에 삽입하여, 베네수엘라 말뇌염 바이러스 유사 입자의 발현을 위한 플라스미드 (이하 VEEV-VLP74 또는 78 로 지칭됨) 를 구축하였고, 여기서 개질된 VLP74 또는 78-유래 펩티드는 베네수엘라 말뇌염 바이러스 구조 폴리펩티드의 E2 에 삽입되었다.
PEI (GE Healthcare) 또는 GeneX (ATCC) 를 사용하여 293F 세포 (Lifetechnology) 를 플라스미드로 트랜스펙션하였다. 트랜스펙션 후 4 일차에, 조정 배지를 수집하고, 3000rpm 에서 15 분 동안 원심분리하여, 이를 세포로부터 분리시켰다. 0.45 ㎛ 필터를 사용하여 상청액을 여과하여, 바이러스 유사 입자를 수득하였다. 바이러스 유사 입자를 TFF 컬럼을 사용하여 농축시키고, QXL 컬럼 (GE Healthcare) 을 사용하여 정제하여, 정제된 바이러스 유사 입자를 수득하였다. 동물이 바이러스 유사 입자로 면역화되는 경우, 정제된 바이러스 유사 입자를 스핀 컬럼 (분자량-차단: 100kDa) 을 사용하여 추가로 농축시켜, 면역화를 위한 바이러스 유사 입자를 제조하였다.
VEEV 특이적 항제 및 VLP74 또는 78 특이적 항체를 사용하여 웨스턴 블롯에 의해, 베네수엘라 말뇌염 바이러스 구조 폴리펩티드와 공액된 VLP74　또는 78 을 포함하는 VLP 의 발현을 확인하였다.
실시예 3: 비(非)인간 영장류 (원숭이) 에서의 면역원성
보조제 (Sigma Adjuvant System, Sigma, S6322) 포함 또는 미포함하여 근육내 주사에 의해, 원숭이를 0 주차에 x25-CHI (80ug) 로 및 3 주차에 x6-VEE (80ug) 로 면역화하였다. X25-CHI 는 CHIKV VLP 입자 상에의 25 회 말라리아 CSP 반복 아미노산 NPNA (VLP78_15) 를 의미한다. X6-VEE 는 VEEV VLP 입자 상에의 6 회 말라리아 CSP 반복 아미노산 NPNA (VLP74_25) 를 의미한다. 1 차 면역화 후 2 및 5 주차에 혈액을 채취하였다.
96 웰 ELISA 플레이트를 100ul PBS 완충액 중의 50ng 의 재조합 포자소체 단백질 (rCSP) (Reagent Proteins, ATG-422) 로 사전에 잘 코팅하였다. 2 시간 인큐베이션 후, 상기 플레이트를 0.05% Tween-20 함유 TBS 완충액으로 3 회 세정하고, 0.05% Tween-20 및 5% 분유 함유 TBS 완충액으로 차단하였다. 원숭이의 열 비활성화 희석 혈청을 차단 완충액에 첨가하고, 실온에서 1 시간 동안 인큐베이션하였다. 3 회 세정 후, 퍼옥시다아제 라벨된 염소 항-인간 IgG 또는 항-마우스 IgG 를 1:4000 희석으로 첨가하고, 실온에서 1 시간 동안 인큐베이션하였다. 3 회 세정 후, 발달을 위해 퍼옥시다아제 기질을 첨가하고, 10 분 동안 인큐베이션한 후, 2N H2SO4 를 첨가하여 발달을 중단시켰다. Gen5 (BioTek) 및 GraphPad Prism6 (GraphPad software Inc) 을 사용하여 데이터를 분석하였다.
면역원성은 도 4 내지 6 에 제시되어 있다.
CSP 에 대한 항체의 유도가 말라리아 VLP 로 면역화된 모든 원숭이 혈청에서 확인되었다 (도 4 참조). CSP 에 대한 항체의 역가를 나타내는 평균 OD 값은 도 5 에 제시되어 있다. 도 5 는, 면역화된 원숭이의 혈청이 CSP 에 대한 항체의 고 역가를 유도했다는 것을 나타낸다.
도 6 에 제시된 바와 같이, NPNA 를 포함하는 CHIKV VLP 입자 및 NPNA 를 포함하는 VEEV VLP 입자가, 각각, 면역화의 프라이밍 및 면역화의 부스팅에 사용되는 경우, 오로지 NPNA 를 포함하는 CHIKV VLP 입자가 면역화의 프라이밍 및 면역화의 부스팅 둘 모두에 사용되었던 경우에 비해, CSP 에 대한 항체의 보다 높은 역가가 달성되었다. 또한, 도 6 은, 보조제의 사용이 CSP 에 대한 항체의 역가를 보다 증진시켰다는 것을 나타낸다. 나아가, 도 6 은, 25-회 반복 NPNA 의 투여가 6-회 반복 NPNA 의 투여보다, CSP 에 대한 항체의 보다 높은 역가를 유도한다는 것을 나타낸다.
보조제의 사용 없이 0 주차에 x25-CHI (80ug) 로 및 3 주차에 x6-VEE (80ug) 로 면역화된 원숭이의 혈청 내 항-Pf CSP 항체 역가를, Malaria Serology Lab Malaria Vaccine Branch, WRAIR 에서 ELISA 로 측정하였다. Malaria Serology Lab Malaria Vaccine Branch, WRAIR 에서 수행된 ELISA 에서, 플레이트를 CSPrp ((NPNA)6 Peptide) [0.2㎍/μL] (제조사: Eurogentec EP070034) 로 코팅하고, 염소 α-인간 IgG (KPL/074-1002 LOT# 120714) 를 제 2 항체로서 사용하였다. 1.0 의 OD 를 산출하는 희석 인자로 최종 역가를 측정하였다 (414nm).
결과적으로, 원숭이의 혈청 내 항-Pf CSP 항체 역가는 1 차 면역화에 비해, 2 차 면역화 후 증진되었다 (표 2 참조). RTS,S (GlaxoSmithKline) 로 면역화된 원숭이의 혈청 내 항-Pf CSP 항체 역가에 비해, 보조제 없이 x25-CHI (80ug) 및 x6-VEE (80ug) 로 면역화된 원숭이의 혈청 내 항-Pf CSP 항체 역가가, RTS,S (GlaxoSmithKline) 가 보조제를 함유하고 있음에도, 보다 더 높은것으로 여겨졌다.
Figure pat00011
실시예 4: 마우스에서의 면역원성
보조제 (Sigma Adjuvant System, Sigma, S6322) 를 포함 또는 미포함하여 근육내 주사에 의해, 마우스를 0 주차에 10ug 의 VLP78_15 로, 3 주차에 10ug 의 VLP74_25 로 및 6 주차에 10ug 의 VLP78_15 로 면역화하였다.
면역화된 마우스의 혈청 내 항-Pf CSP 항체 역가를 Malaria Serology Lab Malaria Vaccine Branch, WRAIR 에서 ELISA 로 측정하였고, 여기서 플레이트를 CSPrp ((NPNA)6 Peptide) [0.2㎍/μL] (제조사: Eurogentec EP070034) 로 코팅하고, 염소 α-마우스 IgG (KPL/074-1806 LOT# 100737) 를 제 2 항체로서 사용하여, 혈청 내 항체를 검출하였다.
1.0 의 OD 를 산출하는 희석 인자로 최종 역가를 측정하였다 (414nm).
면역원성은 표 3 및 4 에 제시되어 있다.
표 3 및 4 는, 바이러스 유사 입자의 3 회 면역화 후, CSP 에 대한 항체의 보다 높은 역가가 달성되었다는 것을 나타낸다. 또한, 표 3 및 4 는, 보조제의 사용이 CSP 에 대한 항체의 역가를 증진시켰다는 것을 나타낸다.
Figure pat00012
Figure pat00013
실시예 5: 마우스에서의 P. yoelii CSP 삽입된 VLP 의 면역원성
설치류 말라리아 CSP (P. yoelii CSP) 에서 확인되는 QGPGAP 를 항원으로 사용하였다. 6x QGPGAP 를 CHIKV VLP 내에 삽입하였다. 보조제 Ribi 를 포함 또는 미포함하여 근육내 주사에 의해, 마우스를 0 및 8 주차에 2 회 CHIKV VLP (마우스 당 20ug VLP) 로 면역화하였다.
1 차 면역화 후 4, 6, 10 및 14 주차에 면역원성을 확인하였다. 항-P. yoelii CSP 항체를 ELISA 로 측정하였다. 플레이트를 0.1 ng/㎕ 로의 P. yoelii CSP 반복 서열 펩티드로 코팅한 것을 제외하고는, 실시예 3 에 기재된 ELISA 와 동일한 방식으로 ELISA 를 수행하였다. 2 차 항체는 항-마우스 IgG HRP (Cell signal, #7076S) 였다. 결과는 도 7-9 에 제시되어 있다.
도 7-9 은, 6X QGPGAP 를 포함하는 CHIKV VLP 의 근육내 투여에 의해, CSP 에 대한 항체의 보다 높은 역가가 달성되었다는 것을 나타낸다. 또한, 도 7-9 은, 보조제의 사용이 CSP 에 대한 항체의 역가를 증진시켰다는 것을 나타낸다.
실시예 6: P. yoelii CSP 항원결정부: 6x QGPGAP 를 포함하는 CHIKV VLP 의 근육내 주사에 의한 말라리아에 대한 마우스의 보호
6x QGPGAP 를 CHIKV VLP 내에 삽입하였다. 보조제 Ribi 를 포함 또는 미포함하여 근육내 주사에 의해, 마우스 (n=5) 를 0 및 8 주차에 2 회 CHIKV VLP (마우스 당 20ug VLP) 로 면역화하였다 (도 10 참조). 설치류 말라리아: P. yoelii-접종 (i.v.) 을 17 주차에 수행하였다 (도 10 참조).
말라리아 감염을 PCR 로 확인하였다. 접종 6 일 후, 게놈 DNA 를 마우스 혈액으로부터 정제하였다. 18S 말라리아 DNA 를 PCR 로 증폭시켰다. 도 11 은 PCR 의 결과를 나타내는 것으로, 이는 5 마리 대조군 마우스 (PBS 주입) 모두 말라리아에 감염되었고; 대조군 VLP 로 면역화된 5 마리 마우스 모두 말라리아에 감염되었고; 6x QGPGAP 를 포함하는 CHIKV VLP 로 면역화된 5 마리 마우스 중에서, 2 마리 마우스는 말라리아에 감염되었고, 3 마리 마우스는 말라리아에 감염되지 않았고; 보조제: Ribi 및 6x QGPGAP 를 포함하는 CHIKV VLP 로 면역화된 5 마리 마우스 중에서, 1 마리 마우스는 말라리아에 감염되었고, 4 마리 마우스는 말라리아에 감염되지 않았다는 것을 나타낸다.
실시예 7: NPNA 반복을 포함하는 치쿤군야 바이러스 (CHIKV) 유사 입자 또는 NPNA 반복을 포함하는 베네수엘라 말뇌염 바이러스 (VEEV) 유사 입자를 포함하는 백신 조성물의 제조
6x 또는 25x NPNA 를 포함하는 치쿤군야 바이러스 (CHIKV) 유사 입자를 실시예 1 에 따라 제조하고, 6x NPNA 를 포함하는 베네수엘라 말뇌염 바이러스 (VEEV) 유사 입자를 실시예 2 에 따라 제조하였다.
백신 조성물을 제조하기 위하여, 각각의 제조된 입자 80μg 을 1ml 의 수크로오스 포스페이트 용액, pH 7.2, 엔도톡신 미포함 (Endotoxin Free) (Teknova, SP 완충액) 과 혼합하였다.
SEQUENCE LISTING <110> VLP THERAPEUTICS, LLC <120> MALARIA VACCINE <130> 672014 <160> 56 <170> PatentIn version 3.5 <210> 1 <211> 1248 <212> PRT <213> Chikungunya virus <400> 1 Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro 1 5 10 15 Arg Pro Trp Thr Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30 Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45 Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60 Arg Lys Asn Lys Lys Gln Lys Gln Lys Gln Gln Ala Pro Gln Asn Asn 65 70 75 80 Thr Asn Gln Lys Lys Gln Pro Pro Lys Lys Lys Pro Ala Gln Lys Lys 85 90 95 Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110 Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Thr Gly Tyr Ala Cys 115 120 125 Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140 Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr 145 150 155 160 Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175 Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190 Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205 Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220 Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu 225 230 235 240 Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255 Gly Ala Glu Glu Trp Ser Leu Ala Ile Pro Val Met Cys Leu Leu Ala 260 265 270 Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285 Glu Lys Glu Pro Glu Glu Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300 Arg Pro Gly Tyr Tyr Gln Leu Leu Gln Ala Ser Leu Thr Cys Ser Pro 305 310 315 320 His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335 Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350 Cys His Ser Pro Val Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365 Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380 Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Asn His Met Pro 385 390 395 400 Ala Asp Ala Glu Arg Ala Gly Leu Phe Val Arg Thr Ser Ala Pro Cys 405 410 415 Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430 Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445 Ser Cys Thr His Pro Phe His His Asp Pro Pro Val Ile Gly Arg Glu 450 455 460 Lys Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr 465 470 475 480 Tyr Val Gln Ser Thr Ala Ala Thr Thr Glu Glu Ile Glu Val His Met 485 490 495 Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Ser Gln Gln Ser Gly Asn 500 505 510 Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525 Gly Gly Ser Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn 530 535 540 Cys Lys Val Asp Gln Cys His Ala Ala Val Thr Asn His Lys Lys Trp 545 550 555 560 Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg 565 570 575 Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg 580 585 590 Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val 595 600 605 Ile Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn 610 615 620 Met Gly Glu Glu Pro Asn Tyr Gln Glu Glu Trp Val Met His Lys Lys 625 630 635 640 Glu Val Val Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly 645 650 655 Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Leu Ser Thr Asn Gly Thr 660 665 670 Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr 675 680 685 Pro Thr Met Thr Val Val Val Val Ser Val Ala Thr Phe Ile Leu Leu 690 695 700 Ser Met Val Gly Met Ala Ala Gly Met Cys Met Cys Ala Arg Arg Arg 705 710 715 720 Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu 725 730 735 Leu Ser Leu Ile Cys Cys Ile Arg Thr Ala Lys Ala Ala Thr Tyr Gln 740 745 750 Glu Ala Ala Ile Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu 755 760 765 Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu 770 775 780 Arg Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met 785 790 795 800 Ser Val Gly Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile 805 810 815 Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly 820 825 830 Tyr Ser Pro Met Val Leu Glu Met Glu Leu Leu Ser Val Thr Leu Glu 835 840 845 Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile 850 855 860 Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys 865 870 875 880 Asn Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe 885 890 895 Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu 900 905 910 Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala 915 920 925 Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val 930 935 940 Leu Tyr Gln Gly Asn Asn Ile Thr Val Thr Ala Tyr Ala Asn Gly Asp 945 950 955 960 His Ala Val Thr Val Lys Asp Ala Lys Phe Ile Val Gly Pro Met Ser 965 970 975 Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp 980 985 990 Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 995 1000 1005 Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1010 1015 1020 Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Val Gly Thr Val 1025 1030 1035 His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1040 1045 1050 Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1055 1060 1065 Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly 1070 1075 1080 Asn Met Pro Ile Ser Ile Asp Ile Pro Glu Ala Ala Phe Thr Arg 1085 1090 1095 Val Val Asp Ala Pro Ser Leu Thr Asp Met Ser Cys Glu Val Pro 1100 1105 1110 Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1115 1120 1125 Tyr Ala Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1130 1135 1140 Asn Ala Val Thr Ile Arg Glu Ala Glu Ile Glu Val Glu Gly Asn 1145 1150 1155 Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu 1160 1165 1170 Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Glu 1175 1180 1185 Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1190 1195 1200 Thr Thr Leu Gly Val Gln Asp Ile Ser Ala Thr Ala Met Ser Trp 1205 1210 1215 Val Gln Lys Ile Thr Gly Gly Val Gly Leu Val Val Ala Val Ala 1220 1225 1230 Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1235 1240 1245 <210> 2 <211> 1248 <212> PRT <213> Chikungunya virus <400> 2 Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro 1 5 10 15 Arg Pro Trp Ala Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30 Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45 Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60 Arg Lys Asn Lys Lys Gln Arg Gln Lys Lys Gln Ala Pro Gln Asn Asp 65 70 75 80 Pro Lys Gln Lys Lys Gln Pro Pro Gln Lys Lys Pro Ala Gln Lys Lys 85 90 95 Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110 Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Met Gly Tyr Ala Cys 115 120 125 Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140 Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr 145 150 155 160 Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175 Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190 Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205 Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220 Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu 225 230 235 240 Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255 Gly Ala Glu Glu Trp Ser Leu Ala Leu Pro Val Leu Cys Leu Leu Ala 260 265 270 Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285 Glu Lys Glu Pro Glu Ser Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300 Arg Pro Gly Tyr Tyr Gln Leu Leu Lys Ala Ser Leu Thr Cys Ser Pro 305 310 315 320 His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335 Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350 Cys His Ser Pro Ile Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365 Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380 Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Ser His Thr Pro 385 390 395 400 Ala Asp Ala Glu Arg Ala Gly Leu Leu Val Arg Thr Ser Ala Pro Cys 405 410 415 Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430 Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445 Thr Cys Thr His Pro Phe His His Glu Pro Pro Val Ile Gly Arg Glu 450 455 460 Arg Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr 465 470 475 480 Tyr Val Gln Ser Thr Ala Ala Thr Ala Glu Glu Ile Glu Val His Met 485 490 495 Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Thr Gln Gln Ser Gly Asn 500 505 510 Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525 Gly Gly Ser Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn 530 535 540 Cys Lys Ile Asp Gln Cys His Ala Ala Val Thr Asn His Lys Asn Trp 545 550 555 560 Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg 565 570 575 Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg 580 585 590 Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val 595 600 605 Thr Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn 610 615 620 Met Gly Gln Glu Pro Asn Tyr His Glu Glu Trp Val Thr His Lys Lys 625 630 635 640 Glu Val Thr Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly 645 650 655 Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Met Ser Thr Asn Gly Thr 660 665 670 Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr 675 680 685 Pro Thr Met Thr Val Val Ile Val Ser Val Ala Ser Phe Val Leu Leu 690 695 700 Ser Met Val Gly Thr Ala Val Gly Met Cys Val Cys Ala Arg Arg Arg 705 710 715 720 Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu 725 730 735 Leu Ser Leu Leu Cys Cys Val Arg Thr Thr Lys Ala Ala Thr Tyr Tyr 740 745 750 Glu Ala Ala Ala Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu 755 760 765 Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu 770 775 780 Lys Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met 785 790 795 800 Ser Ile Gly Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile 805 810 815 Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly 820 825 830 Tyr Ser Pro Met Val Leu Glu Met Glu Leu Gln Ser Val Thr Leu Glu 835 840 845 Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile 850 855 860 Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys 865 870 875 880 Ser Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe 885 890 895 Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu 900 905 910 Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala 915 920 925 Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val 930 935 940 Leu Tyr Gln Gly Asn Asn Ile Thr Val Ala Ala Tyr Ala Asn Gly Asp 945 950 955 960 His Ala Val Thr Val Lys Asp Ala Lys Phe Val Val Gly Pro Met Ser 965 970 975 Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp 980 985 990 Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 995 1000 1005 Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1010 1015 1020 Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Ala Gly Thr Val 1025 1030 1035 His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1040 1045 1050 Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1055 1060 1065 Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly 1070 1075 1080 Asn Ile Pro Ile Ser Ile Asp Ile Pro Asp Ala Ala Phe Thr Arg 1085 1090 1095 Val Val Asp Ala Pro Ser Val Thr Asp Met Ser Cys Glu Val Pro 1100 1105 1110 Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1115 1120 1125 Tyr Thr Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1130 1135 1140 Asn Ala Val Thr Ile Arg Glu Ala Asp Val Glu Val Glu Gly Asn 1145 1150 1155 Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu 1160 1165 1170 Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Ala 1175 1180 1185 Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1190 1195 1200 Thr Thr Leu Gly Val Gln Asp Ile Ser Thr Thr Ala Met Ser Trp 1205 1210 1215 Val Gln Lys Ile Thr Gly Gly Val Gly Leu Ile Val Ala Val Ala 1220 1225 1230 Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1235 1240 1245 <210> 3 <211> 1255 <212> PRT <213> Venesuelan equine encephalitis virus <400> 3 Met Phe Pro Phe Gln Pro Met Tyr Pro Met Gln Pro Met Pro Tyr Arg 1 5 10 15 Asn Pro Phe Ala Ala Pro Arg Arg Pro Trp Phe Pro Arg Thr Asp Pro 20 25 30 Phe Leu Ala Met Gln Val Gln Glu Leu Thr Arg Ser Met Ala Asn Leu 35 40 45 Thr Phe Lys Gln Arg Arg Asp Ala Pro Pro Glu Gly Pro Ser Ala Ala 50 55 60 Lys Pro Lys Lys Glu Ala Ser Gln Lys Gln Lys Gly Gly Gly Gln Gly 65 70 75 80 Lys Lys Lys Lys Asn Gln Gly Lys Lys Lys Ala Lys Thr Gly Pro Pro 85 90 95 Asn Pro Lys Ala Gln Asn Gly Asn Lys Lys Lys Thr Asn Lys Lys Pro 100 105 110 Gly Lys Arg Gln Arg Met Val Met Lys Leu Glu Ser Asp Lys Thr Phe 115 120 125 Pro Ile Met Leu Glu Gly Lys Ile Asn Gly Tyr Ala Cys Val Val Gly 130 135 140 Gly Lys Leu Phe Arg Pro Met His Val Glu Gly Lys Ile Asp Asn Asp 145 150 155 160 Val Leu Ala Ala Leu Lys Thr Lys Lys Ala Ser Lys Tyr Asp Leu Glu 165 170 175 Tyr Ala Asp Val Pro Gln Asn Met Arg Ala Asp Thr Phe Lys Tyr Thr 180 185 190 His Glu Lys Pro Gln Gly Tyr Tyr Ser Trp His His Gly Ala Val Gln 195 200 205 Tyr Glu Asn Gly Arg Phe Thr Val Pro Lys Gly Val Gly Ala Lys Gly 210 215 220 Asp Ser Gly Arg Pro Ile Leu Asp Asn Gln Gly Arg Val Val Ala Ile 225 230 235 240 Val Leu Gly Gly Val Asn Glu Gly Ser Arg Thr Ala Leu Ser Val Val 245 250 255 Met Trp Asn Glu Lys Gly Val Thr Val Lys Tyr Thr Pro Glu Asn Cys 260 265 270 Glu Gln Trp Ser Leu Val Thr Thr Met Cys Leu Leu Ala Asn Val Thr 275 280 285 Phe Pro Cys Ala Gln Pro Pro Ile Cys Tyr Asp Arg Lys Pro Ala Glu 290 295 300 Thr Leu Ala Met Leu Ser Val Asn Val Asp Asn Pro Gly Tyr Asp Glu 305 310 315 320 Leu Leu Glu Ala Ala Val Lys Cys Pro Gly Arg Lys Arg Arg Ser Thr 325 330 335 Glu Glu Leu Phe Asn Glu Tyr Lys Leu Thr Arg Pro Tyr Met Ala Arg 340 345 350 Cys Ile Arg Cys Ala Val Gly Ser Cys His Ser Pro Ile Ala Ile Glu 355 360 365 Ala Val Lys Ser Asp Gly His Asp Gly Tyr Val Arg Leu Gln Thr Ser 370 375 380 Ser Gln Tyr Gly Leu Asp Ser Ser Gly Asn Leu Lys Gly Arg Thr Met 385 390 395 400 Arg Tyr Asp Met His Gly Thr Ile Lys Glu Ile Pro Leu His Gln Val 405 410 415 Ser Leu Tyr Thr Ser Arg Pro Cys His Ile Val Asp Gly His Gly Tyr 420 425 430 Phe Leu Leu Ala Arg Cys Pro Ala Gly Asp Ser Ile Thr Met Glu Phe 435 440 445 Lys Lys Asp Ser Val Arg His Ser Cys Ser Val Pro Tyr Glu Val Lys 450 455 460 Phe Asn Pro Val Gly Arg Glu Leu Tyr Thr His Pro Pro Glu His Gly 465 470 475 480 Val Glu Gln Ala Cys Gln Val Tyr Ala His Asp Ala Gln Asn Arg Gly 485 490 495 Ala Tyr Val Glu Met His Leu Pro Gly Ser Glu Val Asp Ser Ser Leu 500 505 510 Val Ser Leu Ser Gly Ser Ser Val Thr Val Thr Pro Pro Asp Gly Thr 515 520 525 Ser Ala Leu Val Glu Cys Glu Cys Gly Gly Thr Lys Ile Ser Glu Thr 530 535 540 Ile Asn Lys Thr Lys Gln Phe Ser Gln Cys Thr Lys Lys Glu Gln Cys 545 550 555 560 Arg Ala Tyr Arg Leu Gln Asn Asp Lys Trp Val Tyr Asn Ser Asp Lys 565 570 575 Leu Pro Lys Ala Ala Gly Ala Thr Leu Lys Gly Lys Leu His Val Pro 580 585 590 Phe Leu Leu Ala Asp Gly Lys Cys Thr Val Pro Leu Ala Pro Glu Pro 595 600 605 Met Ile Thr Phe Gly Phe Arg Ser Val Ser Leu Lys Leu His Pro Lys 610 615 620 Asn Pro Thr Tyr Leu Ile Thr Arg Gln Leu Ala Asp Glu Pro His Tyr 625 630 635 640 Thr His Glu Leu Ile Ser Glu Pro Ala Val Arg Asn Phe Thr Val Thr 645 650 655 Glu Lys Gly Trp Glu Phe Val Trp Gly Asn His Pro Pro Lys Arg Phe 660 665 670 Trp Ala Gln Glu Thr Ala Pro Gly Asn Pro His Gly Leu Pro His Glu 675 680 685 Val Ile Thr His Tyr Tyr His Arg Tyr Pro Met Ser Thr Ile Leu Gly 690 695 700 Leu Ser Ile Cys Ala Ala Ile Ala Thr Val Ser Val Ala Ala Ser Thr 705 710 715 720 Trp Leu Phe Cys Arg Ser Arg Val Ala Cys Leu Thr Pro Tyr Arg Leu 725 730 735 Thr Pro Asn Ala Arg Ile Pro Phe Cys Leu Ala Val Leu Cys Cys Ala 740 745 750 Arg Thr Ala Arg Ala Glu Thr Thr Trp Glu Ser Leu Asp His Leu Trp 755 760 765 Asn Asn Asn Gln Gln Met Phe Trp Ile Gln Leu Leu Ile Pro Leu Ala 770 775 780 Ala Leu Ile Val Val Thr Arg Leu Leu Arg Cys Val Cys Cys Val Val 785 790 795 800 Pro Phe Leu Val Met Ala Gly Ala Ala Gly Ala Gly Ala Tyr Glu His 805 810 815 Ala Thr Thr Met Pro Ser Gln Ala Gly Ile Ser Tyr Asn Thr Ile Val 820 825 830 Asn Arg Ala Gly Tyr Ala Pro Leu Pro Ile Ser Ile Thr Pro Thr Lys 835 840 845 Ile Lys Leu Ile Pro Thr Val Asn Leu Glu Tyr Val Thr Cys His Tyr 850 855 860 Lys Thr Gly Met Asp Ser Pro Ala Ile Lys Cys Cys Gly Ser Gln Glu 865 870 875 880 Cys Thr Pro Thr Tyr Arg Pro Asp Glu Gln Cys Lys Val Phe Thr Gly 885 890 895 Val Tyr Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Thr Glu 900 905 910 Asn Thr Gln Val Ser Lys Ala Tyr Val Met Lys Ser Asp Asp Cys Leu 915 920 925 Ala Asp His Ala Glu Ala Tyr Lys Ala His Thr Ala Ser Val Gln Ala 930 935 940 Phe Leu Asn Ile Thr Val Gly Glu His Ser Ile Val Thr Thr Val Tyr 945 950 955 960 Val Asn Gly Glu Thr Pro Val Asn Phe Asn Gly Val Lys Ile Thr Ala 965 970 975 Gly Pro Leu Ser Thr Ala Trp Thr Pro Phe Asp Arg Lys Ile Val Gln 980 985 990 Tyr Ala Gly Glu Ile Tyr Asn Tyr Asp Phe Pro Glu Tyr Gly Ala Gly 995 1000 1005 Gln Pro Gly Ala Phe Gly Asp Ile Gln Ser Arg Thr Val Ser Ser 1010 1015 1020 Ser Asp Leu Tyr Ala Asn Thr Asn Leu Val Leu Gln Arg Pro Lys 1025 1030 1035 Ala Gly Ala Ile His Val Pro Tyr Thr Gln Ala Pro Ser Gly Phe 1040 1045 1050 Glu Gln Trp Lys Lys Asp Lys Ala Pro Ser Leu Lys Phe Thr Ala 1055 1060 1065 Pro Phe Gly Cys Glu Ile Tyr Thr Asn Pro Ile Arg Ala Glu Asn 1070 1075 1080 Cys Ala Val Gly Ser Ile Pro Leu Ala Phe Asp Ile Pro Asp Ala 1085 1090 1095 Leu Phe Thr Arg Val Ser Glu Thr Pro Thr Leu Ser Ala Ala Glu 1100 1105 1110 Cys Thr Leu Asn Glu Cys Val Tyr Ser Ser Asp Phe Gly Gly Ile 1115 1120 1125 Ala Thr Val Lys Tyr Ser Ala Ser Lys Ser Gly Lys Cys Ala Val 1130 1135 1140 His Val Pro Ser Gly Thr Ala Thr Leu Lys Glu Ala Ala Val Glu 1145 1150 1155 Leu Thr Glu Gln Gly Ser Ala Thr Ile His Phe Ser Thr Ala Asn 1160 1165 1170 Ile His Pro Glu Phe Arg Leu Gln Ile Cys Thr Ser Tyr Val Thr 1175 1180 1185 Cys Lys Gly Asp Cys His Pro Pro Lys Asp His Ile Val Thr His 1190 1195 1200 Pro Gln Tyr His Ala Gln Thr Phe Thr Ala Ala Val Ser Lys Thr 1205 1210 1215 Ala Trp Thr Trp Leu Thr Ser Leu Leu Gly Gly Ser Ala Val Ile 1220 1225 1230 Ile Ile Ile Gly Leu Val Leu Ala Thr Ile Val Ala Met Tyr Val 1235 1240 1245 Leu Thr Asn Gln Lys His Asn 1250 1255 <210> 4 <211> 2964 <212> DNA <213> Chikungunya virus <400> 4 atgagcctcg ccctcccggt cttgtgcctg ttggcaaaca ctacattccc ctgctctcag 60 ccgccttgca caccctgctg ctacgaaaag gaaccggaaa gcaccttgcg catgcttgag 120 gacaacgtga tgagacccgg atactaccag ctactaaaag catcgctgac ttgctctccc 180 caccgccaaa gacgcagtac taaggacaat tttaatgtct ataaagccac aagaccatat 240 ctagctcatt gtcctgactg cggagaaggg cattcgtgcc acagccctat cgcattggag 300 cgcatcagaa atgaagcaac ggacggaacg ctgaaaatcc aggtctcttt gcagatcggg 360 ataaagacag atgacagcca cgattggacc aagctgcgct atatggatag ccatacgcca 420 gcggacgcgg agcgagccgg attgcttgta aggacttcag caccgtgcac gatcaccggg 480 accatgggac actttattct cgcccgatgc ccgaaaggag agacgctgac agtgggattt 540 acggacagca gaaagatcag ccacacatgc acacacccgt tccatcatga accacctgtg 600 ataggtaggg agaggttcca ctctcgacca caacatggta aagagttacc ttgcagcacg 660 tacgtgcaga gcaccgctgc cactgctgag gagatagagg tgcatatgcc cccagatact 720 cctgaccgca cgctgatgac gcagcagtct ggcaacgtga agatcacagt taatgggcag 780 acggtgcggt acaagtgcaa ctgcggtggc tcaaacgagg gactgacaac cacagacaaa 840 gtgatcaata actgcaaaat tgatcagtgc catgctgcag tcactaatca caagaattgg 900 caatacaact cccctttagt cccgcgcaac gctgaactcg gggaccgtaa aggaaagatc 960 cacatcccat tcccattggc aaacgtgact tgcagagtgc caaaagcaag aaaccctaca 1020 gtaacttacg gaaaaaacca agtcaccatg ctgctgtatc ctgaccatcc gacactcttg 1080 tcttaccgta acatgggaca ggaaccaaat taccacgagg agtgggtgac acacaagaag 1140 gaggttacct tgaccgtgcc tactgagggt ctggaggtca cttggggcaa caacgaacca 1200 tacaagtact ggccgcagat gtctacgaac ggtactgctc atggtcaccc acatgagata 1260 atcttgtact attatgagct gtaccccact atgactgtag tcattgtgtc ggtggcctcg 1320 ttcgtgcttc tgtcgatggt gggcacagca gtgggaatgt gtgtgtgcgc acggcgcaga 1380 tgcattacac catatgaatt aacaccagga gccactgttc ccttcctgct cagcctgcta 1440 tgctgcgtca gaacgaccaa ggcggccaca tattacgagg ctgcggcata tctatggaac 1500 gaacagcagc ccctgttctg gttgcaggct cttatcccgc tggccgcctt gatcgtcctg 1560 tgcaactgtc tgaaactctt gccatgctgc tgtaagaccc tggctttttt agccgtaatg 1620 agcatcggtg cccacactgt gagcgcgtac gaacacgtaa cagtgatccc gaacacggtg 1680 ggagtaccgt ataagactct tgtcaacaga ccgggttaca gccccatggt gttggagatg 1740 gagctacaat cagtcacctt ggaaccaaca ctgtcacttg actacatcac gtgcgagtac 1800 aaaactgtca tcccctcccc gtacgtgaag tgctgtggta cagcagagtg caaggacaag 1860 agcctaccag actacagctg caaggtcttt actggagtct acccatttat gtggggcggc 1920 gcctactgct tttgcgacgc cgaaaatacg caattgagcg aggcacatgt agagaaatct 1980 gaatcttgca aaacagagtt tgcatcggcc tacagagccc acaccgcatc ggcgtcggcg 2040 aagctccgcg tcctttacca aggaaacaac attaccgtag ctgcctacgc taacggtgac 2100 catgccgtca cagtaaagga cgccaagttt gtcgtgggcc caatgtcctc cgcctggaca 2160 ccttttgaca acaaaatcgt ggtgtacaaa ggcgacgtct acaacatgga ctacccacct 2220 tttggcgcag gaagaccagg acaatttggt gacattcaaa gtcgtacacc ggaaagtaaa 2280 gacgtttatg ccaacactca gttggtacta cagaggccag cagcaggcac ggtacatgta 2340 ccatactctc aggcaccatc tggcttcaag tattggctga aggaacgagg agcatcgcta 2400 cagcacacgg caccgttcgg ttgccagatt gcgacaaacc cggtaagagc tgtaaattgc 2460 gctgtgggga acataccaat ttccatcgac ataccggatg cggcctttac tagggttgtc 2520 gatgcaccct ctgtaacgga catgtcatgc gaagtaccag cctgcactca ctcctccgac 2580 tttgggggcg tcgccatcat caaatacaca gctagcaaga aaggtaaatg tgcagtacat 2640 tcgatgacca acgccgttac cattcgagaa gccgacgtag aagtagaggg gaactcccag 2700 ctgcaaatat ccttctcaac agccctggca agcgccgagt ttcgcgtgca agtgtgctcc 2760 acacaagtac actgcgcagc cgcatgccac cctccaaagg accacatagt caattaccca 2820 gcatcacaca ccacccttgg ggtccaggat atatccacaa cggcaatgtc ttgggtgcag 2880 aagattacgg gaggagtagg attaattgtt gctgttgctg ccttaatttt aattgtggtg 2940 ctatgcgtgt cgtttagcag gcac 2964 <210> 5 <211> 2964 <212> DNA <213> Chikungunya virus <400> 5 atgagtcttg ccatcccagt tatgtgcctg ttggcaaaca ccacgttccc ctgctcccag 60 cccccttgca cgccctgctg ctacgaaaag gaaccggagg aaaccctacg catgcttgag 120 gacaacgtca tgagacctgg gtactatcag ctgctacaag catccttaac atgttctccc 180 caccgccagc gacgcagcac caaggacaac ttcaatgtct ataaagccac aagaccatac 240 ttagctcact gtcccgactg tggagaaggg cactcgtgcc atagtcccgt agcactagaa 300 cgcatcagaa atgaagcgac agacgggacg ctgaaaatcc aggtctcctt gcaaatcgga 360 ataaagacgg atgacagcca cgattggacc aagctgcgtt atatggacaa ccacatgcca 420 gcagacgcag agagggcggg gctatttgta agaacatcag caccgtgtac gattactgga 480 acaatgggac acttcatcct ggcccgatgt ccaaaagggg aaactctgac ggtgggattc 540 actgacagta ggaagattag tcactcatgt acgcacccat ttcaccacga ccctcctgtg 600 ataggtcggg aaaaattcca ttcccgaccg cagcacggta aagagctacc ttgcagcacg 660 tacgtgcaga gcaccgccgc aactaccgag gagatagagg tacacatgcc cccagacacc 720 cctgatcgca cattaatgtc acaacagtcc ggcaacgtaa agatcacagt caatggccag 780 acggtgcggt acaagtgtaa ttgcggtggc tcaaatgaag gactaacaac tacagacaaa 840 gtgattaata actgcaaggt tgatcaatgt catgccgcgg tcaccaatca caaaaagtgg 900 cagtataact cccctctggt cccgcgtaat gctgaacttg gggaccgaaa aggaaaaatt 960 cacatcccgt ttccgctggc aaatgtaaca tgcagggtgc ctaaagcaag gaaccccacc 1020 gtgacgtacg ggaaaaacca agtcatcatg ctactgtatc ctgaccaccc aacactcctg 1080 tcctaccgga atatgggaga agaaccaaac tatcaagaag agtgggtgat gcataagaag 1140 gaagtcgtgc taaccgtgcc gactgaaggg ctcgaggtca cgtggggcaa caacgagccg 1200 tataagtatt ggccgcagtt atctacaaac ggtacagccc atggccaccc gcatgagata 1260 attctgtatt attatgagct gtaccccact atgactgtag tagttgtgtc agtggccacg 1320 ttcatactcc tgtcgatggt gggtatggca gcggggatgt gcatgtgtgc acgacgcaga 1380 tgcatcacac cgtatgaact gacaccagga gctaccgtcc ctttcctgct tagcctaata 1440 tgctgcatca gaacagctaa agcggccaca taccaagagg ctgcgatata cctgtggaac 1500 gagcagcaac ctttgttttg gctacaagcc cttattccgc tggcagccct gattgttcta 1560 tgcaactgtc tgagactctt accatgctgc tgtaaaacgt tggctttttt agccgtaatg 1620 agcgtcggtg cccacactgt gagcgcgtac gaacacgtaa cagtgatccc gaacacggtg 1680 ggagtaccgt ataagactct agtcaataga cctggctaca gccccatggt attggagatg 1740 gaactactgt cagtcacttt ggagccaaca ctatcgcttg attacatcac gtgcgagtac 1800 aaaaccgtca tcccgtctcc gtacgtgaag tgctgcggta cagcagagtg caaggacaaa 1860 aacctacctg actacagctg taaggtcttc accggcgtct acccatttat gtggggcggc 1920 gcctactgct tctgcgacgc tgaaaacacg cagttgagcg aagcacacgt ggagaagtcc 1980 gaatcatgca aaacagaatt tgcatcagca tacagggctc ataccgcatc tgcatcagct 2040 aagctccgcg tcctttacca aggaaataac atcactgtaa ctgcctatgc aaacggcgac 2100 catgccgtca cagttaagga cgccaaattc attgtggggc caatgtcttc agcctggaca 2160 cctttcgaca acaaaattgt ggtgtacaaa ggtgacgtct ataacatgga ctacccgccc 2220 tttggcgcag gaagaccagg acaatttggc gatatccaaa gtcgcacacc tgagagtaaa 2280 gacgtctatg ctaatacaca actggtactg cagagaccgg ctgtgggtac ggtacacgtg 2340 ccatactctc aggcaccatc tggctttaag tattggctaa aagaacgcgg ggcgtcgctg 2400 cagcacacag caccatttgg ctgccaaata gcaacaaacc cggtaagagc ggtgaactgc 2460 gccgtaggga acatgcccat ctccatcgac ataccggaag cggccttcac tagggtcgtc 2520 gacgcgccct ctttaacgga catgtcgtgc gaggtaccag cctgcaccca ttcctcagac 2580 tttgggggcg tcgccattat taaatatgca gccagcaaga aaggcaagtg tgcggtgcat 2640 tcgatgacta acgccgtcac tattcgggaa gctgagatag aagttgaagg gaattctcag 2700 ctgcaaatct ctttctcgac ggccttagcc agcgccgaat tccgcgtaca agtctgttct 2760 acacaagtac actgtgcagc cgagtgccac cccccgaagg accacatagt caactacccg 2820 gcgtcacata ccaccctcgg ggtccaggac atctccgcta cggcgatgtc atgggtgcag 2880 aagatcacgg gaggtgtggg actggttgtt gctgttgccg cactgattct aatcgtggtg 2940 ctatgcgtgt cgttcagcag gcac 2964 <210> 6 <211> 3747 <212> DNA <213> Chikungunya virus <400> 6 atggagttca tcccgacgca aactttctat aacagaaggt accaaccccg accctgggcc 60 ccacgcccta caattcaagt aattagacct agaccacgtc cacagaggca ggctgggcaa 120 ctcgcccagc tgatctccgc agtcaacaaa ttgaccatgc gcgcggtacc tcaacagaag 180 cctcgcagaa atcggaaaaa caagaagcaa aggcagaaga agcaggcgcc gcaaaacgac 240 ccaaagcaaa agaagcaacc accacaaaag aagccggctc aaaagaagaa gaaaccaggc 300 cgtagggaga gaatgtgcat gaaaattgaa aatgattgca tcttcgaagt caagcatgaa 360 ggcaaagtga tgggctacgc atgcctggtg ggggataaag taatgaaacc agcacatgtg 420 aagggaacta tcgacaatgc cgatctggct aaactggcct ttaagcggtc gtctaaatac 480 gatcttgaat gtgcacagat accggtgcac atgaagtctg atgcctcgaa gtttacccac 540 gagaaacccg aggggtacta taactggcat cacggagcag tgcagtattc aggaggccgg 600 ttcactatcc cgacgggtgc aggcaagccg ggagacagcg gcagaccgat cttcgacaac 660 aaaggacggg tggtggccat cgtcctagga ggggccaacg aaggtgcccg cacggccctc 720 tccgtggtga cgtggaacaa agacatcgtc acaaaaatta cccctgaggg agccgaagag 780 tggagcctcg ccctcccggt cttgtgcctg ttggcaaaca ctacattccc ctgctctcag 840 ccgccttgca caccctgctg ctacgaaaag gaaccggaaa gcaccttgcg catgcttgag 900 gacaacgtga tgagacccgg atactaccag ctactaaaag catcgctgac ttgctctccc 960 caccgccaaa gacgcagtac taaggacaat tttaatgtct ataaagccac aagaccatat 1020 ctagctcatt gtcctgactg cggagaaggg cattcgtgcc acagccctat cgcattggag 1080 cgcatcagaa atgaagcaac ggacggaacg ctgaaaatcc aggtctcttt gcagatcggg 1140 ataaagacag atgacagcca cgattggacc aagctgcgct atatggatag ccatacgcca 1200 gcggacgcgg agcgagccgg attgcttgta aggacttcag caccgtgcac gatcaccggg 1260 accatgggac actttattct cgcccgatgc ccgaaaggag agacgctgac agtgggattt 1320 acggacagca gaaagatcag ccacacatgc acacacccgt tccatcatga accacctgtg 1380 ataggtaggg agaggttcca ctctcgacca caacatggta aagagttacc ttgcagcacg 1440 tacgtgcaga gcaccgctgc cactgctgag gagatagagg tgcatatgcc cccagatact 1500 cctgaccgca cgctgatgac gcagcagtct ggcaacgtga agatcacagt taatgggcag 1560 acggtgcggt acaagtgcaa ctgcggtggc tcaaacgagg gactgacaac cacagacaaa 1620 gtgatcaata actgcaaaat tgatcagtgc catgctgcag tcactaatca caagaattgg 1680 caatacaact cccctttagt cccgcgcaac gctgaactcg gggaccgtaa aggaaagatc 1740 cacatcccat tcccattggc aaacgtgact tgcagagtgc caaaagcaag aaaccctaca 1800 gtaacttacg gaaaaaacca agtcaccatg ctgctgtatc ctgaccatcc gacactcttg 1860 tcttaccgta acatgggaca ggaaccaaat taccacgagg agtgggtgac acacaagaag 1920 gaggttacct tgaccgtgcc tactgagggt ctggaggtca cttggggcaa caacgaacca 1980 tacaagtact ggccgcagat gtctacgaac ggtactgctc atggtcaccc acatgagata 2040 atcttgtact attatgagct gtaccccact atgactgtag tcattgtgtc ggtggcctcg 2100 ttcgtgcttc tgtcgatggt gggcacagca gtgggaatgt gtgtgtgcgc acggcgcaga 2160 tgcattacac catatgaatt aacaccagga gccactgttc ccttcctgct cagcctgcta 2220 tgctgcgtca gaacgaccaa ggcggccaca tattacgagg ctgcggcata tctatggaac 2280 gaacagcagc ccctgttctg gttgcaggct cttatcccgc tggccgcctt gatcgtcctg 2340 tgcaactgtc tgaaactctt gccatgctgc tgtaagaccc tggctttttt agccgtaatg 2400 agcatcggtg cccacactgt gagcgcgtac gaacacgtaa cagtgatccc gaacacggtg 2460 ggagtaccgt ataagactct tgtcaacaga ccgggttaca gccccatggt gttggagatg 2520 gagctacaat cagtcacctt ggaaccaaca ctgtcacttg actacatcac gtgcgagtac 2580 aaaactgtca tcccctcccc gtacgtgaag tgctgtggta cagcagagtg caaggacaag 2640 agcctaccag actacagctg caaggtcttt actggagtct acccatttat gtggggcggc 2700 gcctactgct tttgcgacgc cgaaaatacg caattgagcg aggcacatgt agagaaatct 2760 gaatcttgca aaacagagtt tgcatcggcc tacagagccc acaccgcatc ggcgtcggcg 2820 aagctccgcg tcctttacca aggaaacaac attaccgtag ctgcctacgc taacggtgac 2880 catgccgtca cagtaaagga cgccaagttt gtcgtgggcc caatgtcctc cgcctggaca 2940 ccttttgaca acaaaatcgt ggtgtacaaa ggcgacgtct acaacatgga ctacccacct 3000 tttggcgcag gaagaccagg acaatttggt gacattcaaa gtcgtacacc ggaaagtaaa 3060 gacgtttatg ccaacactca gttggtacta cagaggccag cagcaggcac ggtacatgta 3120 ccatactctc aggcaccatc tggcttcaag tattggctga aggaacgagg agcatcgcta 3180 cagcacacgg caccgttcgg ttgccagatt gcgacaaacc cggtaagagc tgtaaattgc 3240 gctgtgggga acataccaat ttccatcgac ataccggatg cggcctttac tagggttgtc 3300 gatgcaccct ctgtaacgga catgtcatgc gaagtaccag cctgcactca ctcctccgac 3360 tttgggggcg tcgccatcat caaatacaca gctagcaaga aaggtaaatg tgcagtacat 3420 tcgatgacca acgccgttac cattcgagaa gccgacgtag aagtagaggg gaactcccag 3480 ctgcaaatat ccttctcaac agccctggca agcgccgagt ttcgcgtgca agtgtgctcc 3540 acacaagtac actgcgcagc cgcatgccac cctccaaagg accacatagt caattaccca 3600 gcatcacaca ccacccttgg ggtccaggat atatccacaa cggcaatgtc ttgggtgcag 3660 aagattacgg gaggagtagg attaattgtt gctgttgctg ccttaatttt aattgtggtg 3720 ctatgcgtgt cgtttagcag gcactaa 3747 <210> 7 <211> 3747 <212> DNA <213> Chikungunya virus <400> 7 atggagttca tcccaaccca aactttttac aataggaggt accagcctcg accctggact 60 ccgcgcccta ctatccaagt catcaggccc agaccgcgcc ctcagaggca agctgggcaa 120 cttgcccagc tgatctcagc agttaataaa ctgacaatgc gcgcggtacc acaacagaag 180 ccacgcagga atcggaagaa taagaagcaa aagcaaaaac aacaggcgcc acaaaacaac 240 acaaatcaaa agaagcagcc acctaaaaag aaaccggctc aaaagaaaaa gaagccgggc 300 cgcagagaga ggatgtgcat gaaaatcgaa aatgattgta ttttcgaagt caagcacgaa 360 ggtaaggtaa caggttacgc gtgcctggtg ggggacaaag taatgaaacc agcacacgta 420 aaggggacca tcgataacgc ggacctggcc aaactggcct ttaagcggtc atctaagtat 480 gaccttgaat gcgcgcagat acccgtgcac atgaagtccg acgcttcgaa gttcacccat 540 gagaaaccgg aggggtacta caactggcac cacggagcag tacagtactc aggaggccgg 600 ttcaccatcc ctacaggtgc tggcaaacca ggggacagcg gcagaccgat cttcgacaac 660 aagggacgcg tggtggccat agtcttagga ggagctaatg aaggagcccg tacagccctc 720 tcggtggtga cctggaataa agacattgtc actaaaatca cccccgaggg ggccgaagag 780 tggagtcttg ccatcccagt tatgtgcctg ttggcaaaca ccacgttccc ctgctcccag 840 cccccttgca cgccctgctg ctacgaaaag gaaccggagg aaaccctacg catgcttgag 900 gacaacgtca tgagacctgg gtactatcag ctgctacaag catccttaac atgttctccc 960 caccgccagc gacgcagcac caaggacaac ttcaatgtct ataaagccac aagaccatac 1020 ttagctcact gtcccgactg tggagaaggg cactcgtgcc atagtcccgt agcactagaa 1080 cgcatcagaa atgaagcgac agacgggacg ctgaaaatcc aggtctcctt gcaaatcgga 1140 ataaagacgg atgacagcca cgattggacc aagctgcgtt atatggacaa ccacatgcca 1200 gcagacgcag agagggcggg gctatttgta agaacatcag caccgtgtac gattactgga 1260 acaatgggac acttcatcct ggcccgatgt ccaaaagggg aaactctgac ggtgggattc 1320 actgacagta ggaagattag tcactcatgt acgcacccat ttcaccacga ccctcctgtg 1380 ataggtcggg aaaaattcca ttcccgaccg cagcacggta aagagctacc ttgcagcacg 1440 tacgtgcaga gcaccgccgc aactaccgag gagatagagg tacacatgcc cccagacacc 1500 cctgatcgca cattaatgtc acaacagtcc ggcaacgtaa agatcacagt caatggccag 1560 acggtgcggt acaagtgtaa ttgcggtggc tcaaatgaag gactaacaac tacagacaaa 1620 gtgattaata actgcaaggt tgatcaatgt catgccgcgg tcaccaatca caaaaagtgg 1680 cagtataact cccctctggt cccgcgtaat gctgaacttg gggaccgaaa aggaaaaatt 1740 cacatcccgt ttccgctggc aaatgtaaca tgcagggtgc ctaaagcaag gaaccccacc 1800 gtgacgtacg ggaaaaacca agtcatcatg ctactgtatc ctgaccaccc aacactcctg 1860 tcctaccgga atatgggaga agaaccaaac tatcaagaag agtgggtgat gcataagaag 1920 gaagtcgtgc taaccgtgcc gactgaaggg ctcgaggtca cgtggggcaa caacgagccg 1980 tataagtatt ggccgcagtt atctacaaac ggtacagccc atggccaccc gcatgagata 2040 attctgtatt attatgagct gtaccccact atgactgtag tagttgtgtc agtggccacg 2100 ttcatactcc tgtcgatggt gggtatggca gcggggatgt gcatgtgtgc acgacgcaga 2160 tgcatcacac cgtatgaact gacaccagga gctaccgtcc ctttcctgct tagcctaata 2220 tgctgcatca gaacagctaa agcggccaca taccaagagg ctgcgatata cctgtggaac 2280 gagcagcaac ctttgttttg gctacaagcc cttattccgc tggcagccct gattgttcta 2340 tgcaactgtc tgagactctt accatgctgc tgtaaaacgt tggctttttt agccgtaatg 2400 agcgtcggtg cccacactgt gagcgcgtac gaacacgtaa cagtgatccc gaacacggtg 2460 ggagtaccgt ataagactct agtcaataga cctggctaca gccccatggt attggagatg 2520 gaactactgt cagtcacttt ggagccaaca ctatcgcttg attacatcac gtgcgagtac 2580 aaaaccgtca tcccgtctcc gtacgtgaag tgctgcggta cagcagagtg caaggacaaa 2640 aacctacctg actacagctg taaggtcttc accggcgtct acccatttat gtggggcggc 2700 gcctactgct tctgcgacgc tgaaaacacg cagttgagcg aagcacacgt ggagaagtcc 2760 gaatcatgca aaacagaatt tgcatcagca tacagggctc ataccgcatc tgcatcagct 2820 aagctccgcg tcctttacca aggaaataac atcactgtaa ctgcctatgc aaacggcgac 2880 catgccgtca cagttaagga cgccaaattc attgtggggc caatgtcttc agcctggaca 2940 cctttcgaca acaaaattgt ggtgtacaaa ggtgacgtct ataacatgga ctacccgccc 3000 tttggcgcag gaagaccagg acaatttggc gatatccaaa gtcgcacacc tgagagtaaa 3060 gacgtctatg ctaatacaca actggtactg cagagaccgg ctgtgggtac ggtacacgtg 3120 ccatactctc aggcaccatc tggctttaag tattggctaa aagaacgcgg ggcgtcgctg 3180 cagcacacag caccatttgg ctgccaaata gcaacaaacc cggtaagagc ggtgaactgc 3240 gccgtaggga acatgcccat ctccatcgac ataccggaag cggccttcac tagggtcgtc 3300 gacgcgccct ctttaacgga catgtcgtgc gaggtaccag cctgcaccca ttcctcagac 3360 tttgggggcg tcgccattat taaatatgca gccagcaaga aaggcaagtg tgcggtgcat 3420 tcgatgacta acgccgtcac tattcgggaa gctgagatag aagttgaagg gaattctcag 3480 ctgcaaatct ctttctcgac ggccttagcc agcgccgaat tccgcgtaca agtctgttct 3540 acacaagtac actgtgcagc cgagtgccac cccccgaagg accacatagt caactacccg 3600 gcgtcacata ccaccctcgg ggtccaggac atctccgcta cggcgatgtc atgggtgcag 3660 aagatcacgg gaggtgtggg actggttgtt gctgttgccg cactgattct aatcgtggtg 3720 ctatgcgtgt cgttcagcag gcactaa 3747 <210> 8 <211> 8404 <212> DNA <213> Artificial <220> <223> VLP_CHI512 vector <400> 8 gaattcccat tgcatacgtt gtatccatat cataatatgt acatttatat tggctcatgt 60 ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta atcaattacg 120 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 180 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 240 atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 300 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 360 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 420 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 480 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 540 gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 600 tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 660 gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt tgacctccat 720 agaagacacc gggaccgatc cagcctccgt taacggtgga gggcagtgta gtctgagcag 780 tactcgttgc tgccgcgcgc gccaccagac ataatagctg acagactaac agactgttcc 840 tttccatggg tcttttctgc agtcaccgtc gtcgacacgt gtgatcagat atcgcggccg 900 ccaccatgga gttcatcccg acgcaaactt tctataacag aaggtaccaa ccccgaccct 960 gggccccacg ccctacaatt caagtaatta gacctagacc acgtccacag aggcaggctg 1020 ggcaactcgc ccagctgatc tccgcagtca acaaattgac catgcgcgcg gtacctcaac 1080 agaagcctcg cagaaatcgg aaaaacaaga agcaaaggca gaagaagcag gcgccgcaaa 1140 acgacccaaa gcaaaagaag caaccaccac aaaagaagcc ggctcaaaag aagaagaaac 1200 caggccgtag ggagagaatg tgcatgaaaa ttgaaaatga ttgcatcttc gaagtcaagc 1260 atgaaggcaa agtgatgggc tacgcatgcc tggtggggga taaagtaatg aaaccagcac 1320 atgtgaaggg aactatcgac aatgccgatc tggctaaact ggcctttaag cggtcgtcta 1380 aatacgatct tgaatgtgca cagataccgg tgcacatgaa gtctgatgcc tcgaagttta 1440 cccacgagaa acccgagggg tactataact ggcatcacgg agcagtgcag tattcaggag 1500 gccggttcac tatcccgacg ggtgcaggca agccgggaga cagcggcaga ccgatcttcg 1560 acaacaaagg acgggtggtg gccatcgtcc taggaggggc caacgaaggt gcccgcacgg 1620 ccctctccgt ggtgacgtgg aacaaagaca tcgtcacaaa aattacccct gagggagccg 1680 aagagtggag cctcgccctc ccggtcttgt gcctgttggc aaacactaca ttcccctgct 1740 ctcagccgcc ttgcacaccc tgctgctacg aaaaggaacc ggaaagcacc ttgcgcatgc 1800 ttgaggacaa cgtgatgaga cccggatact accagctact aaaagcatcg ctgacttgct 1860 ctccccaccg ccaaagacgc agtactaagg acaattttaa tgtctataaa gccacaagac 1920 catatctagc tcattgtcct gactgcggag aagggcattc gtgccacagc cctatcgcat 1980 tggagcgcat cagaaatgaa gcaacggacg gaacgctgaa aatccaggtc tctttgcaga 2040 tcgggataaa gacagatgac agccacgatt ggaccaagct gcgctatatg gatagccata 2100 cgccagcgga cgcggagcga gccggattgc ttgtaaggac ttcagcaccg tgcacgatca 2160 ccgggaccat gggacacttt attctcgccc gatgcccgaa aggagagacg ctgacagtgg 2220 gatttacgga cagcagaaag atcagccaca catgcacaca cccgttccat catgaaccac 2280 ctgtgatagg tagggagagg ttccactctc gaccacaaca tggtaaagag ttaccttgca 2340 gcacgtacgt gcagagcacc gctgccactg ctgaggagat agaggtgcat atgcccccag 2400 atactcctga ccgcacgctg atgacgcagc agtccggagg atccaacgtg aagatcacag 2460 ttaatgggca gacggtgcgg tacaagtgca actgcggtgg ctcaaacgag ggactgacaa 2520 ccacagacaa agtgatcaat aactgcaaaa ttgatcagtg ccatgctgca gtcactaatc 2580 acaagaattg gcaatacaac tcccctttag tcccgcgcaa cgctgaactc ggggaccgta 2640 aaggaaagat ccacatccca ttcccattgg caaacgtgac ttgcagagtg ccaaaagcaa 2700 gaaaccctac agtaacttac ggaaaaaacc aagtcaccat gctgctgtat cctgaccatc 2760 cgacactctt gtcttaccgt aacatgggac aggaaccaaa ttaccacgag gagtgggtga 2820 cacacaagaa ggaggttacc ttgaccgtgc ctactgaggg tctggaggtc acttggggca 2880 acaacgaacc atacaagtac tggccgcaga tgtctacgaa cggtactgct catggtcacc 2940 cacatgagat aatcttgtac tattatgagc tgtaccccac tatgactgta gtcattgtgt 3000 cggtggcctc gttcgtgctt ctgtcgatgg tgggcacagc agtgggaatg tgtgtgtgcg 3060 cacggcgcag atgcattaca ccatatgaat taacaccagg agccactgtt cccttcctgc 3120 tcagcctgct atgctgcgtc agaacgacca aggcggccac atattacgag gctgcggcat 3180 atctatggaa cgaacagcag cccctgttct ggttgcaggc tcttatcccg ctggccgcct 3240 tgatcgtcct gtgcaactgt ctgaaactct tgccatgctg ctgtaagacc ctggcttttt 3300 tagccgtaat gagcatcggt gcccacactg tgagcgcgta cgaacacgta acagtgatcc 3360 cgaacacggt gggagtaccg tataagactc ttgtcaacag accgggttac agccccatgg 3420 tgttggagat ggagctacaa tcagtcacct tggaaccaac actgtcactt gactacatca 3480 cgtgcgagta caaaactgtc atcccctccc cgtacgtgaa gtgctgtggt acagcagagt 3540 gcaaggacaa gagcctacca gactacagct gcaaggtctt tactggagtc tacccattta 3600 tgtggggcgg cgcctactgc ttttgcgacg ccgaaaatac gcaattgagc gaggcacatg 3660 tagagaaatc tgaatcttgc aaaacagagt ttgcatcggc ctacagagcc cacaccgcat 3720 cggcgtcggc gaagctccgc gtcctttacc aaggaaacaa cattaccgta gctgcctacg 3780 ctaacggtga ccatgccgtc acagtaaagg acgccaagtt tgtcgtgggc ccaatgtcct 3840 ccgcctggac accttttgac aacaaaatcg tggtgtacaa aggcgacgtc tacaacatgg 3900 actacccacc ttttggcgca ggaagaccag gacaatttgg tgacattcaa agtcgtacac 3960 cggaaagtaa agacgtttat gccaacactc agttggtact acagaggcca gcagcaggca 4020 cggtacatgt accatactct caggcaccat ctggcttcaa gtattggctg aaggaacgag 4080 gagcatcgct acagcacacg gcaccgttcg gttgccagat tgcgacaaac ccggtaagag 4140 ctgtaaattg cgctgtgggg aacataccaa tttccatcga cataccggat gcggccttta 4200 ctagggttgt cgatgcaccc tctgtaacgg acatgtcatg cgaagtacca gcctgcactc 4260 actcctccga ctttgggggc gtcgccatca tcaaatacac agctagcaag aaaggtaaat 4320 gtgcagtaca ttcgatgacc aacgccgtta ccattcgaga agccgacgta gaagtagagg 4380 ggaactccca gctgcaaata tccttctcaa cagccctggc aagcgccgag tttcgcgtgc 4440 aagtgtgctc cacacaagta cactgcgcag ccgcatgcca ccctccaaag gaccacatag 4500 tcaattaccc agcatcacac accacccttg gggtccagga tatatccaca acggcaatgt 4560 cttgggtgca gaagattacg ggaggagtag gattaattgt tgctgttgct gccttaattt 4620 taattgtggt gctatgcgtg tcgtttagca ggcactaagg atctagatct gctgtgcctt 4680 ctagttgcca gccatctgtt gtttgcccct cccccgtgcc ttccttgacc ctggaaggtg 4740 ccactcccac tgtcctttcc taataaaatg aggaaattgc atcgcattgt ctgagtaggt 4800 gtcattctat tctggggggt ggggtggggc aggacagcaa gggggaggat tgggaagaca 4860 atagcaggca tgctggggat gcggtgggct ctatgggtac ccaggtgctg aagaattgac 4920 ccggttcctc ctgggccaga aagaagcagg cacatcccct tctctgtgac acaccctgtc 4980 cacgcccctg gttcttagtt ccagccccac tcataggaca ctcatagctc aggagggctc 5040 cgccttcaat cccacccgct aaagtacttg gagcggtctc tccctccctc atcagcccac 5100 caaaccaaac ctagcctcca agagtgggaa gaaattaaag caagataggc tattaagtgc 5160 agagggagag aaaatgcctc caacatgtga ggaagtaatg agagaaatca tagaatttta 5220 aggccatgat ttaaggccat catggcctaa gcttgaaagg agataggatc aaagcttggc 5280 gtaatcatgg tcatagctgt ttcctgtgtg aaattgttat ccgctcacaa ttccacacaa 5340 catacgagcc ggaagcataa agtgtaaagc ctggggtgcc taatgagtga gctaactcac 5400 attaattgcg ttgcgctcac tgcccgcttt ccagtcggga aacctgtcgt gccagctgca 5460 ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct cttccgcttc 5520 ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat cagctcactc 5580 aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga acatgtgagc 5640 aaaaggccag caaaaggcca ggaaccgtaa aaaggccgcg ttgctggcgt ttttccatag 5700 gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt ggcgaaaccc 5760 gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc gctctcctgt 5820 tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa gcgtggcgct 5880 ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct ccaagctggg 5940 ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta actatcgtct 6000 tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg gtaacaggat 6060 tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc ctaactacgg 6120 ctacactaga agaacagtat ttggtatctg cgctctgctg aagccagtta ccttcggaaa 6180 aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg gtttttttgt 6240 ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt tgatcttttc 6300 tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg tcatgagatt 6360 atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta aatcaatcta 6420 aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg aggcacctat 6480 ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg tgtagataac 6540 tacgatacgg gagggcttac catctggccc cagtgctgca atgataccgc gagaaccacg 6600 ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg agcgcagaag 6660 tggtcctgca actttatccg cctccatcca gtctattaat tgttgccggg aagctagagt 6720 aagtagttcg ccagttaata gtttgcgcaa cgttgttgcc attgctacag gcatcgtggt 6780 gtcacgctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat caaggcgagt 6840 tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc cgatcgttgt 6900 cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc ataattctct 6960 tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa ccaagtcatt 7020 ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac gggataatac 7080 cgcgccacat agcagaactt taaaagtgct catcattgga aaacgttctt cggggcgaaa 7140 actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc gtgcacccaa 7200 ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa caggaaggca 7260 aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca tactcttcct 7320 ttttcaatat tattgaagca tttatcaggg ttattgtctc atgagcggat acatatttga 7380 atgtatttag aaaaataaac aaataggggt tccgcgcaca tttccccgaa aagtgccacc 7440 tgacgtctaa gaaaccatta ttatcatgac attaacctat aaaaataggc gtatcacgag 7500 gccctttcgg gtcgcgcgtt tcggtgatga cggtgaaaac ctctgacaca tgcagctccc 7560 gttgacggtc acagcttgtc tgtaagcgga tgccgggagc agacaagccc gtcagggcgc 7620 gtcagcgggt gttggcgggt gtcggggctg gcttaactat gcggcatcag agcagattgt 7680 actgagagtg caccataaaa ttgtaaacgt taatattttg ttaaaattcg cgttaaattt 7740 ttgttaaatc agctcatttt ttaaccaata ggccgaaatc ggcaaaatcc cttataaatc 7800 aaaagaatag cccgagatag ggttgagtgt tgttccagtt tggaacaaga gtccactatt 7860 aaagaacgtg gactccaacg tcaaagggcg aaaaaccgtc tatcagggcg atggcccact 7920 acgtgaacca tcacccaaat caagtttttt ggggtcgagg tgccgtaaag cactaaatcg 7980 gaaccctaaa gggagccccc gatttagagc ttgacgggga aagccggcga acgtggcgag 8040 aaaggaaggg aagaaagcga aaggagcggg cgctagggcg ctggcaagtg tagcggtcac 8100 gctgcgcgta accaccacac ccgccgcgct taatgcgccg ctacagggcg cgtactatgg 8160 ttgctttgac gtatgcggtg tgaaataccg cacagatgcg taaggagaaa ataccgcatc 8220 aggcgccatt cgccattcag gctgcgcaac tgttgggaag ggcgatcggt gcgggcctct 8280 tcgctattac gccagctggc gaaaggggga tgtgctgcaa ggcgattaag ttgggtaacg 8340 ccagggtttt cccagtcacg acgttgtaaa acgacggcca gtgaattcca tggtctcaac 8400 tttc 8404 <210> 9 <211> 8410 <212> DNA <213> Artificial <220> <223> VLP_CHI 532 vector <400> 9 gaattcccat tgcatacgtt gtatccatat cataatatgt acatttatat tggctcatgt 60 ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta atcaattacg 120 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 180 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 240 atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 300 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 360 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 420 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 480 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 540 gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 600 tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 660 gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt tgacctccat 720 agaagacacc gggaccgatc cagcctccgt taacggtgga gggcagtgta gtctgagcag 780 tactcgttgc tgccgcgcgc gccaccagac ataatagctg acagactaac agactgttcc 840 tttccatggg tcttttctgc agtcaccgtc gtcgacacgt gtgatcagat atcgcggccg 900 ccaccatgga gttcatcccg acgcaaactt tctataacag aaggtaccaa ccccgaccct 960 gggccccacg ccctacaatt caagtaatta gacctagacc acgtccacag aggcaggctg 1020 ggcaactcgc ccagctgatc tccgcagtca acaaattgac catgcgcgcg gtacctcaac 1080 agaagcctcg cagaaatcgg aaaaacaaga agcaaaggca gaagaagcag gcgccgcaaa 1140 acgacccaaa gcaaaagaag caaccaccac aaaagaagcc ggctcaaaag aagaagaaac 1200 caggccgtag ggagagaatg tgcatgaaaa ttgaaaatga ttgcatcttc gaagtcaagc 1260 atgaaggcaa agtgatgggc tacgcatgcc tggtggggga taaagtaatg aaaccagcac 1320 atgtgaaggg aactatcgac aatgccgatc tggctaaact ggcctttaag cggtcgtcta 1380 aatacgatct tgaatgtgca cagataccgg tgcacatgaa gtctgatgcc tcgaagttta 1440 cccacgagaa acccgagggg tactataact ggcatcacgg agcagtgcag tattcaggag 1500 gccggttcac tatcccgacg ggtgcaggca agccgggaga cagcggcaga ccgatcttcg 1560 acaacaaagg acgggtggtg gccatcgtcc taggaggggc caacgaaggt gcccgcacgg 1620 ccctctccgt ggtgacgtgg aacaaagaca tcgtcacaaa aattacccct gagggagccg 1680 aagagtggag cctcgccctc ccggtcttgt gcctgttggc aaacactaca ttcccctgct 1740 ctcagccgcc ttgcacaccc tgctgctacg aaaaggaacc ggaaagcacc ttgcgcatgc 1800 ttgaggacaa cgtgatgaga cccggatact accagctact aaaagcatcg ctgacttgct 1860 ctccccaccg ccaaagacgc agtactaagg acaattttaa tgtctataaa gccacaagac 1920 catatctagc tcattgtcct gactgcggag aagggcattc gtgccacagc cctatcgcat 1980 tggagcgcat cagaaatgaa gcaacggacg gaacgctgaa aatccaggtc tctttgcaga 2040 tcgggataaa gacagatgac agccacgatt ggaccaagct gcgctatatg gatagccata 2100 cgccagcgga cgcggagcga gccggattgc ttgtaaggac ttcagcaccg tgcacgatca 2160 ccgggaccat gggacacttt attctcgccc gatgcccgaa aggagagacg ctgacagtgg 2220 gatttacgga cagcagaaag atcagccaca catgcacaca cccgttccat catgaaccac 2280 ctgtgatagg tagggagagg ttccactctc gaccacaaca tggtaaagag ttaccttgca 2340 gcacgtacgt gcagagcacc gctgccactg ctgaggagat agaggtgcat atgcccccag 2400 atactcctga ccgcacgctg atgacgcagc agtctggcaa cgtgaagatc acagttaatg 2460 ggcagacggt gcggtacaag tgcaactgcg gtggctccgg aagtggatcc aacgagggac 2520 tgacaaccac agacaaagtg atcaataact gcaaaattga tcagtgccat gctgcagtca 2580 ctaatcacaa gaattggcaa tacaactccc ctttagtccc gcgcaacgct gaactcgggg 2640 accgtaaagg aaagatccac atcccattcc cattggcaaa cgtgacttgc agagtgccaa 2700 aagcaagaaa ccctacagta acttacggaa aaaaccaagt caccatgctg ctgtatcctg 2760 accatccgac actcttgtct taccgtaaca tgggacagga accaaattac cacgaggagt 2820 gggtgacaca caagaaggag gttaccttga ccgtgcctac tgagggtctg gaggtcactt 2880 ggggcaacaa cgaaccatac aagtactggc cgcagatgtc tacgaacggt actgctcatg 2940 gtcacccaca tgagataatc ttgtactatt atgagctgta ccccactatg actgtagtca 3000 ttgtgtcggt ggcctcgttc gtgcttctgt cgatggtggg cacagcagtg ggaatgtgtg 3060 tgtgcgcacg gcgcagatgc attacaccat atgaattaac accaggagcc actgttccct 3120 tcctgctcag cctgctatgc tgcgtcagaa cgaccaaggc ggccacatat tacgaggctg 3180 cggcatatct atggaacgaa cagcagcccc tgttctggtt gcaggctctt atcccgctgg 3240 ccgccttgat cgtcctgtgc aactgtctga aactcttgcc atgctgctgt aagaccctgg 3300 cttttttagc cgtaatgagc atcggtgccc acactgtgag cgcgtacgaa cacgtaacag 3360 tgatcccgaa cacggtggga gtaccgtata agactcttgt caacagaccg ggttacagcc 3420 ccatggtgtt ggagatggag ctacaatcag tcaccttgga accaacactg tcacttgact 3480 acatcacgtg cgagtacaaa actgtcatcc cctccccgta cgtgaagtgc tgtggtacag 3540 cagagtgcaa ggacaagagc ctaccagact acagctgcaa ggtctttact ggagtctacc 3600 catttatgtg gggcggcgcc tactgctttt gcgacgccga aaatacgcaa ttgagcgagg 3660 cacatgtaga gaaatctgaa tcttgcaaaa cagagtttgc atcggcctac agagcccaca 3720 ccgcatcggc gtcggcgaag ctccgcgtcc tttaccaagg aaacaacatt accgtagctg 3780 cctacgctaa cggtgaccat gccgtcacag taaaggacgc caagtttgtc gtgggcccaa 3840 tgtcctccgc ctggacacct tttgacaaca aaatcgtggt gtacaaaggc gacgtctaca 3900 acatggacta cccacctttt ggcgcaggaa gaccaggaca atttggtgac attcaaagtc 3960 gtacaccgga aagtaaagac gtttatgcca acactcagtt ggtactacag aggccagcag 4020 caggcacggt acatgtacca tactctcagg caccatctgg cttcaagtat tggctgaagg 4080 aacgaggagc atcgctacag cacacggcac cgttcggttg ccagattgcg acaaacccgg 4140 taagagctgt aaattgcgct gtggggaaca taccaatttc catcgacata ccggatgcgg 4200 cctttactag ggttgtcgat gcaccctctg taacggacat gtcatgcgaa gtaccagcct 4260 gcactcactc ctccgacttt gggggcgtcg ccatcatcaa atacacagct agcaagaaag 4320 gtaaatgtgc agtacattcg atgaccaacg ccgttaccat tcgagaagcc gacgtagaag 4380 tagaggggaa ctcccagctg caaatatcct tctcaacagc cctggcaagc gccgagtttc 4440 gcgtgcaagt gtgctccaca caagtacact gcgcagccgc atgccaccct ccaaaggacc 4500 acatagtcaa ttacccagca tcacacacca cccttggggt ccaggatata tccacaacgg 4560 caatgtcttg ggtgcagaag attacgggag gagtaggatt aattgttgct gttgctgcct 4620 taattttaat tgtggtgcta tgcgtgtcgt ttagcaggca ctaaggatct agatctgctg 4680 tgccttctag ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg 4740 aaggtgccac tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga 4800 gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg 4860 aagacaatag caggcatgct ggggatgcgg tgggctctat gggtacccag gtgctgaaga 4920 attgacccgg ttcctcctgg gccagaaaga agcaggcaca tccccttctc tgtgacacac 4980 cctgtccacg cccctggttc ttagttccag ccccactcat aggacactca tagctcagga 5040 gggctccgcc ttcaatccca cccgctaaag tacttggagc ggtctctccc tccctcatca 5100 gcccaccaaa ccaaacctag cctccaagag tgggaagaaa ttaaagcaag ataggctatt 5160 aagtgcagag ggagagaaaa tgcctccaac atgtgaggaa gtaatgagag aaatcataga 5220 attttaaggc catgatttaa ggccatcatg gcctaagctt gaaaggagat aggatccaag 5280 cttggcgtaa tcatggtcat agctgtttcc tgtgtgaaat tgttatccgc tcacaattcc 5340 acacaacata cgagccggaa gcataaagtg taaagcctgg ggtgcctaat gagtgagcta 5400 actcacatta attgcgttgc gctcactgcc cgctttccag tcgggaaacc tgtcgtgcca 5460 gctgcattaa tgaatcggcc aacgcgcggg gagaggcggt ttgcgtattg ggcgctcttc 5520 cgcttcctcg ctcactgact cgctgcgctc ggtcgttcgg ctgcggcgag cggtatcagc 5580 tcactcaaag gcggtaatac ggttatccac agaatcaggg gataacgcag gaaagaacat 5640 gtgagcaaaa ggccagcaaa aggccaggaa ccgtaaaaag gccgcgttgc tggcgttttt 5700 ccataggctc cgcccccctg acgagcatca caaaaatcga cgctcaagtc agaggtggcg 5760 aaacccgaca ggactataaa gataccaggc gtttccccct ggaagctccc tcgtgcgctc 5820 tcctgttccg accctgccgc ttaccggata cctgtccgcc tttctccctt cgggaagcgt 5880 ggcgctttct catagctcac gctgtaggta tctcagttcg gtgtaggtcg ttcgctccaa 5940 gctgggctgt gtgcacgaac cccccgttca gcccgaccgc tgcgccttat ccggtaacta 6000 tcgtcttgag tccaacccgg taagacacga cttatcgcca ctggcagcag ccactggtaa 6060 caggattagc agagcgaggt atgtaggcgg tgctacagag ttcttgaagt ggtggcctaa 6120 ctacggctac actagaagaa cagtatttgg tatctgcgct ctgctgaagc cagttacctt 6180 cggaaaaaga gttggtagct cttgatccgg caaacaaacc accgctggta gcggtggttt 6240 ttttgtttgc aagcagcaga ttacgcgcag aaaaaaagga tctcaagaag atcctttgat 6300 cttttctacg gggtctgacg ctcagtggaa cgaaaactca cgttaaggga ttttggtcat 6360 gagattatca aaaaggatct tcacctagat ccttttaaat taaaaatgaa gttttaaatc 6420 aatctaaagt atatatgagt aaacttggtc tgacagttac caatgcttaa tcagtgaggc 6480 acctatctca gcgatctgtc tatttcgttc atccatagtt gcctgactcc ccgtcgtgta 6540 gataactacg atacgggagg gcttaccatc tggccccagt gctgcaatga taccgcgaga 6600 accacgctca ccggctccag atttatcagc aataaaccag ccagccggaa gggccgagcg 6660 cagaagtggt cctgcaactt tatccgcctc catccagtct attaattgtt gccgggaagc 6720 tagagtaagt agttcgccag ttaatagttt gcgcaacgtt gttgccattg ctacaggcat 6780 cgtggtgtca cgctcgtcgt ttggtatggc ttcattcagc tccggttccc aacgatcaag 6840 gcgagttaca tgatccccca tgttgtgcaa aaaagcggtt agctccttcg gtcctccgat 6900 cgttgtcaga agtaagttgg ccgcagtgtt atcactcatg gttatggcag cactgcataa 6960 ttctcttact gtcatgccat ccgtaagatg cttttctgtg actggtgagt actcaaccaa 7020 gtcattctga gaatagtgta tgcggcgacc gagttgctct tgcccggcgt caatacggga 7080 taataccgcg ccacatagca gaactttaaa agtgctcatc attggaaaac gttcttcggg 7140 gcgaaaactc tcaaggatct taccgctgtt gagatccagt tcgatgtaac ccactcgtgc 7200 acccaactga tcttcagcat cttttacttt caccagcgtt tctgggtgag caaaaacagg 7260 aaggcaaaat gccgcaaaaa agggaataag ggcgacacgg aaatgttgaa tactcatact 7320 cttccttttt caatattatt gaagcattta tcagggttat tgtctcatga gcggatacat 7380 atttgaatgt atttagaaaa ataaacaaat aggggttccg cgcacatttc cccgaaaagt 7440 gccacctgac gtctaagaaa ccattattat catgacatta acctataaaa ataggcgtat 7500 cacgaggccc tttcgggtcg cgcgtttcgg tgatgacggt gaaaacctct gacacatgca 7560 gctcccgttg acggtcacag cttgtctgta agcggatgcc gggagcagac aagcccgtca 7620 gggcgcgtca gcgggtgttg gcgggtgtcg gggctggctt aactatgcgg catcagagca 7680 gattgtactg agagtgcacc ataaaattgt aaacgttaat attttgttaa aattcgcgtt 7740 aaatttttgt taaatcagct cattttttaa ccaataggcc gaaatcggca aaatccctta 7800 taaatcaaaa gaatagcccg agatagggtt gagtgttgtt ccagtttgga acaagagtcc 7860 actattaaag aacgtggact ccaacgtcaa agggcgaaaa accgtctatc agggcgatgg 7920 cccactacgt gaaccatcac ccaaatcaag ttttttgggg tcgaggtgcc gtaaagcact 7980 aaatcggaac cctaaaggga gcccccgatt tagagcttga cggggaaagc cggcgaacgt 8040 ggcgagaaag gaagggaaga aagcgaaagg agcgggcgct agggcgctgg caagtgtagc 8100 ggtcacgctg cgcgtaacca ccacacccgc cgcgcttaat gcgccgctac agggcgcgta 8160 ctatggttgc tttgacgtat gcggtgtgaa ataccgcaca gatgcgtaag gagaaaatac 8220 cgcatcaggc gccattcgcc attcaggctg cgcaactgtt gggaagggcg atcggtgcgg 8280 gcctcttcgc tattacgcca gctggcgaaa gggggatgtg ctgcaaggcg attaagttgg 8340 gtaacgccag ggttttccca gtcacgacgt tgtaaaacga cggccagtga attccatggt 8400 ctcaactttc 8410 <210> 10 <211> 8431 <212> DNA <213> Artificial <220> <223> VLP_VEEV VLP 518 vector <400> 10 gaattcccat tgcatacgtt gtatccatat cataatatgt acatttatat tggctcatgt 60 ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta atcaattacg 120 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 180 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 240 atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 300 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 360 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 420 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 480 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 540 gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 600 tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 660 gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt tgacctccat 720 agaagacacc gggaccgatc cagcctccgt taacggtgga gggcagtgta gtctgagcag 780 tactcgttgc tgccgcgcgc gccaccagac ataatagctg acagactaac agactgttcc 840 tttccatggg tcttttctgc agtcaccgtc gtcgacacgt gtgatcagat atcgcggccg 900 ccaccatgtt cccgttccag ccaatgtatc cgatgcagcc aatgccctat cgcaacccgt 960 tcgcggcccc gcgcaggccc tggttcccca gaaccgaccc ttttctggcg atgcaggtgc 1020 aggaattaac ccgctcgatg gctaacctga cgttcaagca acgccgggac gcgccacctg 1080 aggggccatc cgctaataaa ccgaagaagg aggcctcgca aaaacagaaa gggggaggcc 1140 aagggaagaa gaagaagaac caagggaaga agaaggctaa gacagggccg cctaatccga 1200 aggcacagaa tggaaacaag aagaagacca acaagaaacc aggcaagaga cagcgcatgg 1260 tcatgaaatt ggaatctgac aagacgttcc caatcatgtt ggaagggaag ataaacggct 1320 acgcttgtgt ggtcggaggg aagttattca ggccgatgca tgtggaaggc aagatcgaca 1380 acgacgttct ggccgcgctt aagacgaaga aagcatccaa atacgatctt gagtatgcag 1440 atgtgccaca gaacatgcgg gccgatacat tcaaatacac ccatgagaaa ccccaaggct 1500 attacagctg gcatcatgga gcagtccaat atgaaaatgg gcgtttcacg gtgccgaaag 1560 gagttggggc caagggagac agcggacgac ccattctgga taaccaggga cgggtggtcg 1620 ctattgtgct gggaggtgtg aatgaaggat ctaggacagc cctttcagtc gtcatgtgga 1680 acgagaaggg agttaccgtg aagtatactc cagagaactg cgagcaatgg tcactagtga 1740 ccaccatgtg tctgctcgcc aatgtgacgt tcccatgtgc tcaaccacca atttgctacg 1800 acagaaaacc agcagagact ttggccatgc tcagcgttaa cgttgacaac ccgggctacg 1860 atgagctgct ggaagcagct gttaagtgcc ccggaaggaa aaggagatcc accgaggagc 1920 tgtttaatga gtataagcta acgcgccctt acatggccag atgcatcaga tgtgcagttg 1980 ggagctgcca tagtccaata gcaatcgagg cagtaaagag cgacgggcac gacggttatg 2040 ttagacttca gacttcctcg cagtatggcc tggattcctc cggcaactta aagggcagga 2100 ccatgcggta tgacatgcac gggaccatta aagagatacc actacatcaa gtgtcactct 2160 atacatctcg cccgtgtcac attgtggatg ggcacggtta tttcctgctt gccaggtgcc 2220 cggcagggga ctccatcacc atggaattta agaaagattc cgtcagacac tcctgctcgg 2280 tgccgtatga agtgaaattt aatcctgtag gcagagaact ctatactcat cccccagaac 2340 acggagtaga gcaagcgtgc caagtctacg cacatgatgc acagaacaga ggagcttatg 2400 tcgagatgca cctcccgggc tcagaagtgg acagcagttt ggtttccttg agcggctccg 2460 gaggatccag ttcagtcacc gtgacacctc ctgatgggac tagcgccctg gtggaatgcg 2520 agtgtggcgg cacaaagatc tccgagacca tcaacaagac aaaacagttc agccagtgca 2580 caaagaagga gcagtgcaga gcatatcggc tgcagaacga taagtgggtg tataattctg 2640 acaaactgcc caaagcagcg ggagccacct taaaaggaaa actgcatgtc ccattcttgc 2700 tggcagacgg caaatgcacc gtgcctctag caccagaacc tatgataacc ttcggtttca 2760 gatcagtgtc actgaaactg caccctaaga atcccacata tctaatcacc cgccaacttg 2820 ctgatgagcc tcactacacg cacgagctca tatctgaacc agctgttagg aattttaccg 2880 tcaccgaaaa agggtgggag tttgtatggg gaaaccaccc gccgaaaagg ttttgggcac 2940 aggaaacagc acccggaaat ccacatgggc taccgcacga ggtgataact cattattacc 3000 acagataccc tatgtccacc atcctgggtt tgtcaatttg tgccgccatt gcaaccgttt 3060 ccgttgcagc gtctacctgg ctgttttgca gatcaagagt tgcgtgccta actccttacc 3120 ggctaacacc taacgctagg ataccatttt gtctggctgt gctttgctgc gcccgcactg 3180 cccgggccga gaccacctgg gagtccttgg atcacctatg gaacaataac caacagatgt 3240 tctggattca attgctgatc cctctggccg ccttgatcgt agtgactcgc ctgctcaggt 3300 gcgtgtgctg tgtcgtgcct tttttagtca tggccggcgc cgcaggcgcc ggcgcctacg 3360 agcacgcgac cacgatgccg agccaagcgg gaatctcgta taacactata gtcaacagag 3420 caggctacgc accactccct atcagcataa caccaacaaa gatcaagctg atacctacag 3480 tgaacttgga gtacgtcacc tgccactaca aaacaggaat ggattcacca gccatcaaat 3540 gctgcggatc tcaggaatgc actccaactt acaggcctga tgaacagtgc aaagtcttca 3600 caggggttta cccgttcatg tggggtggtg catattgctt ttgcgacact gagaacaccc 3660 aagtcagcaa ggcctacgta atgaaatctg acgactgcct tgcggatcat gctgaagcat 3720 ataaagcgca cacagcctca gtgcaggcgt tcctcaacat cacagtggga gaacactcta 3780 ttgtgactac cgtgtatgtg aatggagaaa ctcctgtgaa tttcaatggg gtcaaaataa 3840 ctgcaggtcc gctttccaca gcttggacac cctttgatcg caaaatcgtg cagtatgccg 3900 gggagatcta taattatgat tttcctgagt atggggcagg acaaccagga gcatttggag 3960 atatacaatc cagaacagtc tcaagctctg atctgtatgc caataccaac ctagtgctgc 4020 agagacccaa agcaggagcg atccacgtgc catacactca ggcaccttcg ggttttgagc 4080 aatggaagaa agataaagct ccatcattga aatttaccgc ccctttcgga tgcgaaatat 4140 atacaaaccc cattcgcgcc gaaaactgtg ctgtagggtc aattccatta gcctttgaca 4200 ttcccgacgc cttgttcacc agggtgtcag aaacaccgac actttcagcg gccgaatgca 4260 ctcttaacga gtgcgtgtat tcttccgact ttggtgggat cgccacggtc aagtactcgg 4320 ccagcaagtc aggcaagtgc gcagtccatg tgccatcagg gactgctacc ctaaaagaag 4380 cagcagtcga gctaaccgag caagggtcgg cgactatcca tttctcgacc gcaaatatcc 4440 acccggagtt caggctccaa atatgcacat catatgttac gtgcaaaggt gattgtcacc 4500 ccccgaaaga ccatattgtg acacaccctc agtatcacgc ccaaacattt acagccgcgg 4560 tgtcaaaaac cgcgtggacg tggttaacat ccctgctggg aggatcagcc gtaattatta 4620 taattggctt ggtgctggct actattgtgg ccatgtacgt gctgaccaac cagaaacata 4680 attaaggatc tagatctgct gtgccttcta gttgccagcc atctgttgtt tgcccctccc 4740 ccgtgccttc cttgaccctg gaaggtgcca ctcccactgt cctttcctaa taaaatgagg 4800 aaattgcatc gcattgtctg agtaggtgtc attctattct ggggggtggg gtggggcagg 4860 acagcaaggg ggaggattgg gaagacaata gcaggcatgc tggggatgcg gtgggctcta 4920 tgggtaccca ggtgctgaag aattgacccg gttcctcctg ggccagaaag aagcaggcac 4980 atccccttct ctgtgacaca ccctgtccac gcccctggtt cttagttcca gccccactca 5040 taggacactc atagctcagg agggctccgc cttcaatccc acccgctaaa gtacttggag 5100 cggtctctcc ctccctcatc agcccaccaa accaaaccta gcctccaaga gtgggaagaa 5160 attaaagcaa gataggctat taagtgcaga gggagagaaa atgcctccaa catgtgagga 5220 agtaatgaga gaaatcatag aattttaagg ccatgattta aggccatcat ggcctaagct 5280 tgaaaggaga taggatcaaa gcttggcgta atcatggtca tagctgtttc ctgtgtgaaa 5340 ttgttatccg ctcacaattc cacacaacat acgagccgga agcataaagt gtaaagcctg 5400 gggtgcctaa tgagtgagct aactcacatt aattgcgttg cgctcactgc ccgctttcca 5460 gtcgggaaac ctgtcgtgcc agctgcatta atgaatcggc caacgcgcgg ggagaggcgg 5520 tttgcgtatt gggcgctctt ccgcttcctc gctcactgac tcgctgcgct cggtcgttcg 5580 gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca cagaatcagg 5640 ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga accgtaaaaa 5700 ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc acaaaaatcg 5760 acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg cgtttccccc 5820 tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat acctgtccgc 5880 ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt atctcagttc 5940 ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc agcccgaccg 6000 ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg acttatcgcc 6060 actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg gtgctacaga 6120 gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg gtatctgcgc 6180 tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg gcaaacaaac 6240 caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca gaaaaaaagg 6300 atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga acgaaaactc 6360 acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga tccttttaaa 6420 ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt ctgacagtta 6480 ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt catccatagt 6540 tgcctgactc cccgtcgtgt agataactac gatacgggag ggcttaccat ctggccccag 6600 tgctgcaatg ataccgcgag aaccacgctc accggctcca gatttatcag caataaacca 6660 gccagccgga agggccgagc gcagaagtgg tcctgcaact ttatccgcct ccatccagtc 6720 tattaattgt tgccgggaag ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt 6780 tgttgccatt gctacaggca tcgtggtgtc acgctcgtcg tttggtatgg cttcattcag 6840 ctccggttcc caacgatcaa ggcgagttac atgatccccc atgttgtgca aaaaagcggt 6900 tagctccttc ggtcctccga tcgttgtcag aagtaagttg gccgcagtgt tatcactcat 6960 ggttatggca gcactgcata attctcttac tgtcatgcca tccgtaagat gcttttctgt 7020 gactggtgag tactcaacca agtcattctg agaatagtgt atgcggcgac cgagttgctc 7080 ttgcccggcg tcaatacggg ataataccgc gccacatagc agaactttaa aagtgctcat 7140 cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc ttaccgctgt tgagatccag 7200 ttcgatgtaa cccactcgtg cacccaactg atcttcagca tcttttactt tcaccagcgt 7260 ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa aagggaataa gggcgacacg 7320 gaaatgttga atactcatac tcttcctttt tcaatattat tgaagcattt atcagggtta 7380 ttgtctcatg agcggataca tatttgaatg tatttagaaa aataaacaaa taggggttcc 7440 gcgcacattt ccccgaaaag tgccacctga cgtctaagaa accattatta tcatgacatt 7500 aacctataaa aataggcgta tcacgaggcc ctttcgggtc gcgcgtttcg gtgatgacgg 7560 tgaaaacctc tgacacatgc agctcccgtt gacggtcaca gcttgtctgt aagcggatgc 7620 cgggagcaga caagcccgtc agggcgcgtc agcgggtgtt ggcgggtgtc ggggctggct 7680 taactatgcg gcatcagagc agattgtact gagagtgcac cataaaattg taaacgttaa 7740 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta accaataggc 7800 cgaaatcggc aaaatccctt ataaatcaaa agaatagccc gagatagggt tgagtgttgt 7860 tccagtttgg aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 7920 aaccgtctat cagggcgatg gcccactacg tgaaccatca cccaaatcaa gttttttggg 7980 gtcgaggtgc cgtaaagcac taaatcggaa ccctaaaggg agcccccgat ttagagcttg 8040 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggcgc 8100 tagggcgctg gcaagtgtag cggtcacgct gcgcgtaacc accacacccg ccgcgcttaa 8160 tgcgccgcta cagggcgcgt actatggttg ctttgacgta tgcggtgtga aataccgcac 8220 agatgcgtaa ggagaaaata ccgcatcagg cgccattcgc cattcaggct gcgcaactgt 8280 tgggaagggc gatcggtgcg ggcctcttcg ctattacgcc agctggcgaa agggggatgt 8340 gctgcaaggc gattaagttg ggtaacgcca gggttttccc agtcacgacg ttgtaaaacg 8400 acggccagtg aattccatgg tctcaacttt c 8431 <210> 11 <211> 8431 <212> DNA <213> Artificial <220> <223> VLP_VEEV VLP 519 vector <400> 11 gaattcccat tgcatacgtt gtatccatat cataatatgt acatttatat tggctcatgt 60 ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta atcaattacg 120 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 180 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 240 atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 300 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 360 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 420 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 480 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 540 gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 600 tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 660 gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt tgacctccat 720 agaagacacc gggaccgatc cagcctccgt taacggtgga gggcagtgta gtctgagcag 780 tactcgttgc tgccgcgcgc gccaccagac ataatagctg acagactaac agactgttcc 840 tttccatggg tcttttctgc agtcaccgtc gtcgacacgt gtgatcagat atcgcggccg 900 ccaccatgtt cccgttccag ccaatgtatc cgatgcagcc aatgccctat cgcaacccgt 960 tcgcggcccc gcgcaggccc tggttcccca gaaccgaccc ttttctggcg atgcaggtgc 1020 aggaattaac ccgctcgatg gctaacctga cgttcaagca acgccgggac gcgccacctg 1080 aggggccatc cgctaataaa ccgaagaagg aggcctcgca aaaacagaaa gggggaggcc 1140 aagggaagaa gaagaagaac caagggaaga agaaggctaa gacagggccg cctaatccga 1200 aggcacagaa tggaaacaag aagaagacca acaagaaacc aggcaagaga cagcgcatgg 1260 tcatgaaatt ggaatctgac aagacgttcc caatcatgtt ggaagggaag ataaacggct 1320 acgcttgtgt ggtcggaggg aagttattca ggccgatgca tgtggaaggc aagatcgaca 1380 acgacgttct ggccgcgctt aagacgaaga aagcatccaa atacgatctt gagtatgcag 1440 atgtgccaca gaacatgcgg gccgatacat tcaaatacac ccatgagaaa ccccaaggct 1500 attacagctg gcatcatgga gcagtccaat atgaaaatgg gcgtttcacg gtgccgaaag 1560 gagttggggc caagggagac agcggacgac ccattctgga taaccaggga cgggtggtcg 1620 ctattgtgct gggaggtgtg aatgaaggat ctaggacagc cctttcagtc gtcatgtgga 1680 acgagaaggg agttaccgtg aagtatactc cagagaactg cgagcaatgg tcactagtga 1740 ccaccatgtg tctgctcgcc aatgtgacgt tcccatgtgc tcaaccacca atttgctacg 1800 acagaaaacc agcagagact ttggccatgc tcagcgttaa cgttgacaac ccgggctacg 1860 atgagctgct ggaagcagct gttaagtgcc ccggaaggaa aaggagatcc accgaggagc 1920 tgtttaatga gtataagcta acgcgccctt acatggccag atgcatcaga tgtgcagttg 1980 ggagctgcca tagtccaata gcaatcgagg cagtaaagag cgacgggcac gacggttatg 2040 ttagacttca gacttcctcg cagtatggcc tggattcctc cggcaactta aagggcagga 2100 ccatgcggta tgacatgcac gggaccatta aagagatacc actacatcaa gtgtcactct 2160 atacatctcg cccgtgtcac attgtggatg ggcacggtta tttcctgctt gccaggtgcc 2220 cggcagggga ctccatcacc atggaattta agaaagattc cgtcagacac tcctgctcgg 2280 tgccgtatga agtgaaattt aatcctgtag gcagagaact ctatactcat cccccagaac 2340 acggagtaga gcaagcgtgc caagtctacg cacatgatgc acagaacaga ggagcttatg 2400 tcgagatgca cctcccgggc tcagaagtgg acagcagttt ggtttccttg agcggcagtt 2460 ccggaggatc ctcagtcacc gtgacacctc ctgatgggac tagcgccctg gtggaatgcg 2520 agtgtggcgg cacaaagatc tccgagacca tcaacaagac aaaacagttc agccagtgca 2580 caaagaagga gcagtgcaga gcatatcggc tgcagaacga taagtgggtg tataattctg 2640 acaaactgcc caaagcagcg ggagccacct taaaaggaaa actgcatgtc ccattcttgc 2700 tggcagacgg caaatgcacc gtgcctctag caccagaacc tatgataacc ttcggtttca 2760 gatcagtgtc actgaaactg caccctaaga atcccacata tctaatcacc cgccaacttg 2820 ctgatgagcc tcactacacg cacgagctca tatctgaacc agctgttagg aattttaccg 2880 tcaccgaaaa agggtgggag tttgtatggg gaaaccaccc gccgaaaagg ttttgggcac 2940 aggaaacagc acccggaaat ccacatgggc taccgcacga ggtgataact cattattacc 3000 acagataccc tatgtccacc atcctgggtt tgtcaatttg tgccgccatt gcaaccgttt 3060 ccgttgcagc gtctacctgg ctgttttgca gatcaagagt tgcgtgccta actccttacc 3120 ggctaacacc taacgctagg ataccatttt gtctggctgt gctttgctgc gcccgcactg 3180 cccgggccga gaccacctgg gagtccttgg atcacctatg gaacaataac caacagatgt 3240 tctggattca attgctgatc cctctggccg ccttgatcgt agtgactcgc ctgctcaggt 3300 gcgtgtgctg tgtcgtgcct tttttagtca tggccggcgc cgcaggcgcc ggcgcctacg 3360 agcacgcgac cacgatgccg agccaagcgg gaatctcgta taacactata gtcaacagag 3420 caggctacgc accactccct atcagcataa caccaacaaa gatcaagctg atacctacag 3480 tgaacttgga gtacgtcacc tgccactaca aaacaggaat ggattcacca gccatcaaat 3540 gctgcggatc tcaggaatgc actccaactt acaggcctga tgaacagtgc aaagtcttca 3600 caggggttta cccgttcatg tggggtggtg catattgctt ttgcgacact gagaacaccc 3660 aagtcagcaa ggcctacgta atgaaatctg acgactgcct tgcggatcat gctgaagcat 3720 ataaagcgca cacagcctca gtgcaggcgt tcctcaacat cacagtggga gaacactcta 3780 ttgtgactac cgtgtatgtg aatggagaaa ctcctgtgaa tttcaatggg gtcaaaataa 3840 ctgcaggtcc gctttccaca gcttggacac cctttgatcg caaaatcgtg cagtatgccg 3900 gggagatcta taattatgat tttcctgagt atggggcagg acaaccagga gcatttggag 3960 atatacaatc cagaacagtc tcaagctctg atctgtatgc caataccaac ctagtgctgc 4020 agagacccaa agcaggagcg atccacgtgc catacactca ggcaccttcg ggttttgagc 4080 aatggaagaa agataaagct ccatcattga aatttaccgc ccctttcgga tgcgaaatat 4140 atacaaaccc cattcgcgcc gaaaactgtg ctgtagggtc aattccatta gcctttgaca 4200 ttcccgacgc cttgttcacc agggtgtcag aaacaccgac actttcagcg gccgaatgca 4260 ctcttaacga gtgcgtgtat tcttccgact ttggtgggat cgccacggtc aagtactcgg 4320 ccagcaagtc aggcaagtgc gcagtccatg tgccatcagg gactgctacc ctaaaagaag 4380 cagcagtcga gctaaccgag caagggtcgg cgactatcca tttctcgacc gcaaatatcc 4440 acccggagtt caggctccaa atatgcacat catatgttac gtgcaaaggt gattgtcacc 4500 ccccgaaaga ccatattgtg acacaccctc agtatcacgc ccaaacattt acagccgcgg 4560 tgtcaaaaac cgcgtggacg tggttaacat ccctgctggg aggatcagcc gtaattatta 4620 taattggctt ggtgctggct actattgtgg ccatgtacgt gctgaccaac cagaaacata 4680 attaaggatc tagatctgct gtgccttcta gttgccagcc atctgttgtt tgcccctccc 4740 ccgtgccttc cttgaccctg gaaggtgcca ctcccactgt cctttcctaa taaaatgagg 4800 aaattgcatc gcattgtctg agtaggtgtc attctattct ggggggtggg gtggggcagg 4860 acagcaaggg ggaggattgg gaagacaata gcaggcatgc tggggatgcg gtgggctcta 4920 tgggtaccca ggtgctgaag aattgacccg gttcctcctg ggccagaaag aagcaggcac 4980 atccccttct ctgtgacaca ccctgtccac gcccctggtt cttagttcca gccccactca 5040 taggacactc atagctcagg agggctccgc cttcaatccc acccgctaaa gtacttggag 5100 cggtctctcc ctccctcatc agcccaccaa accaaaccta gcctccaaga gtgggaagaa 5160 attaaagcaa gataggctat taagtgcaga gggagagaaa atgcctccaa catgtgagga 5220 agtaatgaga gaaatcatag aattttaagg ccatgattta aggccatcat ggcctaagct 5280 tgaaaggaga taggatcaaa gcttggcgta atcatggtca tagctgtttc ctgtgtgaaa 5340 ttgttatccg ctcacaattc cacacaacat acgagccgga agcataaagt gtaaagcctg 5400 gggtgcctaa tgagtgagct aactcacatt aattgcgttg cgctcactgc ccgctttcca 5460 gtcgggaaac ctgtcgtgcc agctgcatta atgaatcggc caacgcgcgg ggagaggcgg 5520 tttgcgtatt gggcgctctt ccgcttcctc gctcactgac tcgctgcgct cggtcgttcg 5580 gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca cagaatcagg 5640 ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga accgtaaaaa 5700 ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc acaaaaatcg 5760 acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg cgtttccccc 5820 tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat acctgtccgc 5880 ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt atctcagttc 5940 ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc agcccgaccg 6000 ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg acttatcgcc 6060 actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg gtgctacaga 6120 gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg gtatctgcgc 6180 tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg gcaaacaaac 6240 caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca gaaaaaaagg 6300 atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga acgaaaactc 6360 acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga tccttttaaa 6420 ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt ctgacagtta 6480 ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt catccatagt 6540 tgcctgactc cccgtcgtgt agataactac gatacgggag ggcttaccat ctggccccag 6600 tgctgcaatg ataccgcgag aaccacgctc accggctcca gatttatcag caataaacca 6660 gccagccgga agggccgagc gcagaagtgg tcctgcaact ttatccgcct ccatccagtc 6720 tattaattgt tgccgggaag ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt 6780 tgttgccatt gctacaggca tcgtggtgtc acgctcgtcg tttggtatgg cttcattcag 6840 ctccggttcc caacgatcaa ggcgagttac atgatccccc atgttgtgca aaaaagcggt 6900 tagctccttc ggtcctccga tcgttgtcag aagtaagttg gccgcagtgt tatcactcat 6960 ggttatggca gcactgcata attctcttac tgtcatgcca tccgtaagat gcttttctgt 7020 gactggtgag tactcaacca agtcattctg agaatagtgt atgcggcgac cgagttgctc 7080 ttgcccggcg tcaatacggg ataataccgc gccacatagc agaactttaa aagtgctcat 7140 cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc ttaccgctgt tgagatccag 7200 ttcgatgtaa cccactcgtg cacccaactg atcttcagca tcttttactt tcaccagcgt 7260 ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa aagggaataa gggcgacacg 7320 gaaatgttga atactcatac tcttcctttt tcaatattat tgaagcattt atcagggtta 7380 ttgtctcatg agcggataca tatttgaatg tatttagaaa aataaacaaa taggggttcc 7440 gcgcacattt ccccgaaaag tgccacctga cgtctaagaa accattatta tcatgacatt 7500 aacctataaa aataggcgta tcacgaggcc ctttcgggtc gcgcgtttcg gtgatgacgg 7560 tgaaaacctc tgacacatgc agctcccgtt gacggtcaca gcttgtctgt aagcggatgc 7620 cgggagcaga caagcccgtc agggcgcgtc agcgggtgtt ggcgggtgtc ggggctggct 7680 taactatgcg gcatcagagc agattgtact gagagtgcac cataaaattg taaacgttaa 7740 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta accaataggc 7800 cgaaatcggc aaaatccctt ataaatcaaa agaatagccc gagatagggt tgagtgttgt 7860 tccagtttgg aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 7920 aaccgtctat cagggcgatg gcccactacg tgaaccatca cccaaatcaa gttttttggg 7980 gtcgaggtgc cgtaaagcac taaatcggaa ccctaaaggg agcccccgat ttagagcttg 8040 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggcgc 8100 tagggcgctg gcaagtgtag cggtcacgct gcgcgtaacc accacacccg ccgcgcttaa 8160 tgcgccgcta cagggcgcgt actatggttg ctttgacgta tgcggtgtga aataccgcac 8220 agatgcgtaa ggagaaaata ccgcatcagg cgccattcgc cattcaggct gcgcaactgt 8280 tgggaagggc gatcggtgcg ggcctcttcg ctattacgcc agctggcgaa agggggatgt 8340 gctgcaaggc gattaagttg ggtaacgcca gggttttccc agtcacgacg ttgtaaaacg 8400 acggccagtg aattccatgg tctcaacttt c 8431 <210> 12 <211> 8431 <212> DNA <213> Artificial <220> <223> VLP_VEEV VLP 538 vector <400> 12 gaattcccat tgcatacgtt gtatccatat cataatatgt acatttatat tggctcatgt 60 ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta atcaattacg 120 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 180 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 240 atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 300 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 360 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 420 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 480 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 540 gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 600 tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 660 gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt tgacctccat 720 agaagacacc gggaccgatc cagcctccgt taacggtgga gggcagtgta gtctgagcag 780 tactcgttgc tgccgcgcgc gccaccagac ataatagctg acagactaac agactgttcc 840 tttccatggg tcttttctgc agtcaccgtc gtcgacacgt gtgatcagat atcgcggccg 900 ccaccatgtt cccgttccag ccaatgtatc cgatgcagcc aatgccctat cgcaacccgt 960 tcgcggcccc gcgcaggccc tggttcccca gaaccgaccc ttttctggcg atgcaggtgc 1020 aggaattaac ccgctcgatg gctaacctga cgttcaagca acgccgggac gcgccacctg 1080 aggggccatc cgctaataaa ccgaagaagg aggcctcgca aaaacagaaa gggggaggcc 1140 aagggaagaa gaagaagaac caagggaaga agaaggctaa gacagggccg cctaatccga 1200 aggcacagaa tggaaacaag aagaagacca acaagaaacc aggcaagaga cagcgcatgg 1260 tcatgaaatt ggaatctgac aagacgttcc caatcatgtt ggaagggaag ataaacggct 1320 acgcttgtgt ggtcggaggg aagttattca ggccgatgca tgtggaaggc aagatcgaca 1380 acgacgttct ggccgcgctt aagacgaaga aagcatccaa atacgatctt gagtatgcag 1440 atgtgccaca gaacatgcgg gccgatacat tcaaatacac ccatgagaaa ccccaaggct 1500 attacagctg gcatcatgga gcagtccaat atgaaaatgg gcgtttcacg gtgccgaaag 1560 gagttggggc caagggagac agcggacgac ccattctgga taaccaggga cgggtggtcg 1620 ctattgtgct gggaggtgtg aatgaaggat ctaggacagc cctttcagtc gtcatgtgga 1680 acgagaaggg agttaccgtg aagtatactc cagagaactg cgagcaatgg tcactagtga 1740 ccaccatgtg tctgctcgcc aatgtgacgt tcccatgtgc tcaaccacca atttgctacg 1800 acagaaaacc agcagagact ttggccatgc tcagcgttaa cgttgacaac ccgggctacg 1860 atgagctgct ggaagcagct gttaagtgcc ccggaaggaa aaggagatcc accgaggagc 1920 tgtttaatga gtataagcta acgcgccctt acatggccag atgcatcaga tgtgcagttg 1980 ggagctgcca tagtccaata gcaatcgagg cagtaaagag cgacgggcac gacggttatg 2040 ttagacttca gacttcctcg cagtatggcc tggattcctc cggcaactta aagggcagga 2100 ccatgcggta tgacatgcac gggaccatta aagagatacc actacatcaa gtgtcactct 2160 atacatctcg cccgtgtcac attgtggatg ggcacggtta tttcctgctt gccaggtgcc 2220 cggcagggga ctccatcacc atggaattta agaaagattc cgtcagacac tcctgctcgg 2280 tgccgtatga agtgaaattt aatcctgtag gcagagaact ctatactcat cccccagaac 2340 acggagtaga gcaagcgtgc caagtctacg cacatgatgc acagaacaga ggagcttatg 2400 tcgagatgca cctcccgggc tcagaagtgg acagcagttt ggtttccttg agcggcagtt 2460 cagtcaccgt gacacctcct gatgggacta gcgccctggt ggaatgcgag tgtggctccg 2520 gaggatccgg cacaaagatc tccgagacca tcaacaagac aaaacagttc agccagtgca 2580 caaagaagga gcagtgcaga gcatatcggc tgcagaacga taagtgggtg tataattctg 2640 acaaactgcc caaagcagcg ggagccacct taaaaggaaa actgcatgtc ccattcttgc 2700 tggcagacgg caaatgcacc gtgcctctag caccagaacc tatgataacc ttcggtttca 2760 gatcagtgtc actgaaactg caccctaaga atcccacata tctaatcacc cgccaacttg 2820 ctgatgagcc tcactacacg cacgagctca tatctgaacc agctgttagg aattttaccg 2880 tcaccgaaaa agggtgggag tttgtatggg gaaaccaccc gccgaaaagg ttttgggcac 2940 aggaaacagc acccggaaat ccacatgggc taccgcacga ggtgataact cattattacc 3000 acagataccc tatgtccacc atcctgggtt tgtcaatttg tgccgccatt gcaaccgttt 3060 ccgttgcagc gtctacctgg ctgttttgca gatcaagagt tgcgtgccta actccttacc 3120 ggctaacacc taacgctagg ataccatttt gtctggctgt gctttgctgc gcccgcactg 3180 cccgggccga gaccacctgg gagtccttgg atcacctatg gaacaataac caacagatgt 3240 tctggattca attgctgatc cctctggccg ccttgatcgt agtgactcgc ctgctcaggt 3300 gcgtgtgctg tgtcgtgcct tttttagtca tggccggcgc cgcaggcgcc ggcgcctacg 3360 agcacgcgac cacgatgccg agccaagcgg gaatctcgta taacactata gtcaacagag 3420 caggctacgc accactccct atcagcataa caccaacaaa gatcaagctg atacctacag 3480 tgaacttgga gtacgtcacc tgccactaca aaacaggaat ggattcacca gccatcaaat 3540 gctgcggatc tcaggaatgc actccaactt acaggcctga tgaacagtgc aaagtcttca 3600 caggggttta cccgttcatg tggggtggtg catattgctt ttgcgacact gagaacaccc 3660 aagtcagcaa ggcctacgta atgaaatctg acgactgcct tgcggatcat gctgaagcat 3720 ataaagcgca cacagcctca gtgcaggcgt tcctcaacat cacagtggga gaacactcta 3780 ttgtgactac cgtgtatgtg aatggagaaa ctcctgtgaa tttcaatggg gtcaaaataa 3840 ctgcaggtcc gctttccaca gcttggacac cctttgatcg caaaatcgtg cagtatgccg 3900 gggagatcta taattatgat tttcctgagt atggggcagg acaaccagga gcatttggag 3960 atatacaatc cagaacagtc tcaagctctg atctgtatgc caataccaac ctagtgctgc 4020 agagacccaa agcaggagcg atccacgtgc catacactca ggcaccttcg ggttttgagc 4080 aatggaagaa agataaagct ccatcattga aatttaccgc ccctttcgga tgcgaaatat 4140 atacaaaccc cattcgcgcc gaaaactgtg ctgtagggtc aattccatta gcctttgaca 4200 ttcccgacgc cttgttcacc agggtgtcag aaacaccgac actttcagcg gccgaatgca 4260 ctcttaacga gtgcgtgtat tcttccgact ttggtgggat cgccacggtc aagtactcgg 4320 ccagcaagtc aggcaagtgc gcagtccatg tgccatcagg gactgctacc ctaaaagaag 4380 cagcagtcga gctaaccgag caagggtcgg cgactatcca tttctcgacc gcaaatatcc 4440 acccggagtt caggctccaa atatgcacat catatgttac gtgcaaaggt gattgtcacc 4500 ccccgaaaga ccatattgtg acacaccctc agtatcacgc ccaaacattt acagccgcgg 4560 tgtcaaaaac cgcgtggacg tggttaacat ccctgctggg aggatcagcc gtaattatta 4620 taattggctt ggtgctggct actattgtgg ccatgtacgt gctgaccaac cagaaacata 4680 attaaggatc tagatctgct gtgccttcta gttgccagcc atctgttgtt tgcccctccc 4740 ccgtgccttc cttgaccctg gaaggtgcca ctcccactgt cctttcctaa taaaatgagg 4800 aaattgcatc gcattgtctg agtaggtgtc attctattct ggggggtggg gtggggcagg 4860 acagcaaggg ggaggattgg gaagacaata gcaggcatgc tggggatgcg gtgggctcta 4920 tgggtaccca ggtgctgaag aattgacccg gttcctcctg ggccagaaag aagcaggcac 4980 atccccttct ctgtgacaca ccctgtccac gcccctggtt cttagttcca gccccactca 5040 taggacactc atagctcagg agggctccgc cttcaatccc acccgctaaa gtacttggag 5100 cggtctctcc ctccctcatc agcccaccaa accaaaccta gcctccaaga gtgggaagaa 5160 attaaagcaa gataggctat taagtgcaga gggagagaaa atgcctccaa catgtgagga 5220 agtaatgaga gaaatcatag aattttaagg ccatgattta aggccatcat ggcctaagct 5280 tgaaaggaga taggatcaaa gcttggcgta atcatggtca tagctgtttc ctgtgtgaaa 5340 ttgttatccg ctcacaattc cacacaacat acgagccgga agcataaagt gtaaagcctg 5400 gggtgcctaa tgagtgagct aactcacatt aattgcgttg cgctcactgc ccgctttcca 5460 gtcgggaaac ctgtcgtgcc agctgcatta atgaatcggc caacgcgcgg ggagaggcgg 5520 tttgcgtatt gggcgctctt ccgcttcctc gctcactgac tcgctgcgct cggtcgttcg 5580 gctgcggcga gcggtatcag ctcactcaaa ggcggtaata cggttatcca cagaatcagg 5640 ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa aaggccagga accgtaaaaa 5700 ggccgcgttg ctggcgtttt tccataggct ccgcccccct gacgagcatc acaaaaatcg 5760 acgctcaagt cagaggtggc gaaacccgac aggactataa agataccagg cgtttccccc 5820 tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg cttaccggat acctgtccgc 5880 ctttctccct tcgggaagcg tggcgctttc tcatagctca cgctgtaggt atctcagttc 5940 ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa ccccccgttc agcccgaccg 6000 ctgcgcctta tccggtaact atcgtcttga gtccaacccg gtaagacacg acttatcgcc 6060 actggcagca gccactggta acaggattag cagagcgagg tatgtaggcg gtgctacaga 6120 gttcttgaag tggtggccta actacggcta cactagaaga acagtatttg gtatctgcgc 6180 tctgctgaag ccagttacct tcggaaaaag agttggtagc tcttgatccg gcaaacaaac 6240 caccgctggt agcggtggtt tttttgtttg caagcagcag attacgcgca gaaaaaaagg 6300 atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga acgaaaactc 6360 acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga tccttttaaa 6420 ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt ctgacagtta 6480 ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt catccatagt 6540 tgcctgactc cccgtcgtgt agataactac gatacgggag ggcttaccat ctggccccag 6600 tgctgcaatg ataccgcgag aaccacgctc accggctcca gatttatcag caataaacca 6660 gccagccgga agggccgagc gcagaagtgg tcctgcaact ttatccgcct ccatccagtc 6720 tattaattgt tgccgggaag ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt 6780 tgttgccatt gctacaggca tcgtggtgtc acgctcgtcg tttggtatgg cttcattcag 6840 ctccggttcc caacgatcaa ggcgagttac atgatccccc atgttgtgca aaaaagcggt 6900 tagctccttc ggtcctccga tcgttgtcag aagtaagttg gccgcagtgt tatcactcat 6960 ggttatggca gcactgcata attctcttac tgtcatgcca tccgtaagat gcttttctgt 7020 gactggtgag tactcaacca agtcattctg agaatagtgt atgcggcgac cgagttgctc 7080 ttgcccggcg tcaatacggg ataataccgc gccacatagc agaactttaa aagtgctcat 7140 cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc ttaccgctgt tgagatccag 7200 ttcgatgtaa cccactcgtg cacccaactg atcttcagca tcttttactt tcaccagcgt 7260 ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa aagggaataa gggcgacacg 7320 gaaatgttga atactcatac tcttcctttt tcaatattat tgaagcattt atcagggtta 7380 ttgtctcatg agcggataca tatttgaatg tatttagaaa aataaacaaa taggggttcc 7440 gcgcacattt ccccgaaaag tgccacctga cgtctaagaa accattatta tcatgacatt 7500 aacctataaa aataggcgta tcacgaggcc ctttcgggtc gcgcgtttcg gtgatgacgg 7560 tgaaaacctc tgacacatgc agctcccgtt gacggtcaca gcttgtctgt aagcggatgc 7620 cgggagcaga caagcccgtc agggcgcgtc agcgggtgtt ggcgggtgtc ggggctggct 7680 taactatgcg gcatcagagc agattgtact gagagtgcac cataaaattg taaacgttaa 7740 tattttgtta aaattcgcgt taaatttttg ttaaatcagc tcatttttta accaataggc 7800 cgaaatcggc aaaatccctt ataaatcaaa agaatagccc gagatagggt tgagtgttgt 7860 tccagtttgg aacaagagtc cactattaaa gaacgtggac tccaacgtca aagggcgaaa 7920 aaccgtctat cagggcgatg gcccactacg tgaaccatca cccaaatcaa gttttttggg 7980 gtcgaggtgc cgtaaagcac taaatcggaa ccctaaaggg agcccccgat ttagagcttg 8040 acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggcgc 8100 tagggcgctg gcaagtgtag cggtcacgct gcgcgtaacc accacacccg ccgcgcttaa 8160 tgcgccgcta cagggcgcgt actatggttg ctttgacgta tgcggtgtga aataccgcac 8220 agatgcgtaa ggagaaaata ccgcatcagg cgccattcgc cattcaggct gcgcaactgt 8280 tgggaagggc gatcggtgcg ggcctcttcg ctattacgcc agctggcgaa agggggatgt 8340 gctgcaaggc gattaagttg ggtaacgcca gggttttccc agtcacgacg ttgtaaaacg 8400 acggccagtg aattccatgg tctcaacttt c 8431 <210> 13 <211> 3750 <212> DNA <213> Artificial <220> <223> VLP_CHI 512 vector-CHIKV VLP <400> 13 atggagttca tcccgacgca aactttctat aacagaaggt accaaccccg accctgggcc 60 ccacgcccta caattcaagt aattagacct agaccacgtc cacagaggca ggctgggcaa 120 ctcgcccagc tgatctccgc agtcaacaaa ttgaccatgc gcgcggtacc tcaacagaag 180 cctcgcagaa atcggaaaaa caagaagcaa aggcagaaga agcaggcgcc gcaaaacgac 240 ccaaagcaaa agaagcaacc accacaaaag aagccggctc aaaagaagaa gaaaccaggc 300 cgtagggaga gaatgtgcat gaaaattgaa aatgattgca tcttcgaagt caagcatgaa 360 ggcaaagtga tgggctacgc atgcctggtg ggggataaag taatgaaacc agcacatgtg 420 aagggaacta tcgacaatgc cgatctggct aaactggcct ttaagcggtc gtctaaatac 480 gatcttgaat gtgcacagat accggtgcac atgaagtctg atgcctcgaa gtttacccac 540 gagaaacccg aggggtacta taactggcat cacggagcag tgcagtattc aggaggccgg 600 ttcactatcc cgacgggtgc aggcaagccg ggagacagcg gcagaccgat cttcgacaac 660 aaaggacggg tggtggccat cgtcctagga ggggccaacg aaggtgcccg cacggccctc 720 tccgtggtga cgtggaacaa agacatcgtc acaaaaatta cccctgaggg agccgaagag 780 tggagcctcg ccctcccggt cttgtgcctg ttggcaaaca ctacattccc ctgctctcag 840 ccgccttgca caccctgctg ctacgaaaag gaaccggaaa gcaccttgcg catgcttgag 900 gacaacgtga tgagacccgg atactaccag ctactaaaag catcgctgac ttgctctccc 960 caccgccaaa gacgcagtac taaggacaat tttaatgtct ataaagccac aagaccatat 1020 ctagctcatt gtcctgactg cggagaaggg cattcgtgcc acagccctat cgcattggag 1080 cgcatcagaa atgaagcaac ggacggaacg ctgaaaatcc aggtctcttt gcagatcggg 1140 ataaagacag atgacagcca cgattggacc aagctgcgct atatggatag ccatacgcca 1200 gcggacgcgg agcgagccgg attgcttgta aggacttcag caccgtgcac gatcaccggg 1260 accatgggac actttattct cgcccgatgc ccgaaaggag agacgctgac agtgggattt 1320 acggacagca gaaagatcag ccacacatgc acacacccgt tccatcatga accacctgtg 1380 ataggtaggg agaggttcca ctctcgacca caacatggta aagagttacc ttgcagcacg 1440 tacgtgcaga gcaccgctgc cactgctgag gagatagagg tgcatatgcc cccagatact 1500 cctgaccgca cgctgatgac gcagcagtcc ggaggatcca acgtgaagat cacagttaat 1560 gggcagacgg tgcggtacaa gtgcaactgc ggtggctcaa acgagggact gacaaccaca 1620 gacaaagtga tcaataactg caaaattgat cagtgccatg ctgcagtcac taatcacaag 1680 aattggcaat acaactcccc tttagtcccg cgcaacgctg aactcgggga ccgtaaagga 1740 aagatccaca tcccattccc attggcaaac gtgacttgca gagtgccaaa agcaagaaac 1800 cctacagtaa cttacggaaa aaaccaagtc accatgctgc tgtatcctga ccatccgaca 1860 ctcttgtctt accgtaacat gggacaggaa ccaaattacc acgaggagtg ggtgacacac 1920 aagaaggagg ttaccttgac cgtgcctact gagggtctgg aggtcacttg gggcaacaac 1980 gaaccataca agtactggcc gcagatgtct acgaacggta ctgctcatgg tcacccacat 2040 gagataatct tgtactatta tgagctgtac cccactatga ctgtagtcat tgtgtcggtg 2100 gcctcgttcg tgcttctgtc gatggtgggc acagcagtgg gaatgtgtgt gtgcgcacgg 2160 cgcagatgca ttacaccata tgaattaaca ccaggagcca ctgttccctt cctgctcagc 2220 ctgctatgct gcgtcagaac gaccaaggcg gccacatatt acgaggctgc ggcatatcta 2280 tggaacgaac agcagcccct gttctggttg caggctctta tcccgctggc cgccttgatc 2340 gtcctgtgca actgtctgaa actcttgcca tgctgctgta agaccctggc ttttttagcc 2400 gtaatgagca tcggtgccca cactgtgagc gcgtacgaac acgtaacagt gatcccgaac 2460 acggtgggag taccgtataa gactcttgtc aacagaccgg gttacagccc catggtgttg 2520 gagatggagc tacaatcagt caccttggaa ccaacactgt cacttgacta catcacgtgc 2580 gagtacaaaa ctgtcatccc ctccccgtac gtgaagtgct gtggtacagc agagtgcaag 2640 gacaagagcc taccagacta cagctgcaag gtctttactg gagtctaccc atttatgtgg 2700 ggcggcgcct actgcttttg cgacgccgaa aatacgcaat tgagcgaggc acatgtagag 2760 aaatctgaat cttgcaaaac agagtttgca tcggcctaca gagcccacac cgcatcggcg 2820 tcggcgaagc tccgcgtcct ttaccaagga aacaacatta ccgtagctgc ctacgctaac 2880 ggtgaccatg ccgtcacagt aaaggacgcc aagtttgtcg tgggcccaat gtcctccgcc 2940 tggacacctt ttgacaacaa aatcgtggtg tacaaaggcg acgtctacaa catggactac 3000 ccaccttttg gcgcaggaag accaggacaa tttggtgaca ttcaaagtcg tacaccggaa 3060 agtaaagacg tttatgccaa cactcagttg gtactacaga ggccagcagc aggcacggta 3120 catgtaccat actctcaggc accatctggc ttcaagtatt ggctgaagga acgaggagca 3180 tcgctacagc acacggcacc gttcggttgc cagattgcga caaacccggt aagagctgta 3240 aattgcgctg tggggaacat accaatttcc atcgacatac cggatgcggc ctttactagg 3300 gttgtcgatg caccctctgt aacggacatg tcatgcgaag taccagcctg cactcactcc 3360 tccgactttg ggggcgtcgc catcatcaaa tacacagcta gcaagaaagg taaatgtgca 3420 gtacattcga tgaccaacgc cgttaccatt cgagaagccg acgtagaagt agaggggaac 3480 tcccagctgc aaatatcctt ctcaacagcc ctggcaagcg ccgagtttcg cgtgcaagtg 3540 tgctccacac aagtacactg cgcagccgca tgccaccctc caaaggacca catagtcaat 3600 tacccagcat cacacaccac ccttggggtc caggatatat ccacaacggc aatgtcttgg 3660 gtgcagaaga ttacgggagg agtaggatta attgttgctg ttgctgcctt aattttaatt 3720 gtggtgctat gcgtgtcgtt tagcaggcac 3750 <210> 14 <211> 1250 <212> PRT <213> Artificial <220> <223> VLP_CHI 512 vector-CHIKV VLP <400> 14 Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro 1 5 10 15 Arg Pro Trp Ala Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30 Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45 Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60 Arg Lys Asn Lys Lys Gln Arg Gln Lys Lys Gln Ala Pro Gln Asn Asp 65 70 75 80 Pro Lys Gln Lys Lys Gln Pro Pro Gln Lys Lys Pro Ala Gln Lys Lys 85 90 95 Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110 Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Met Gly Tyr Ala Cys 115 120 125 Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140 Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr 145 150 155 160 Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175 Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190 Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205 Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220 Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu 225 230 235 240 Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255 Gly Ala Glu Glu Trp Ser Leu Ala Leu Pro Val Leu Cys Leu Leu Ala 260 265 270 Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285 Glu Lys Glu Pro Glu Ser Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300 Arg Pro Gly Tyr Tyr Gln Leu Leu Lys Ala Ser Leu Thr Cys Ser Pro 305 310 315 320 His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335 Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350 Cys His Ser Pro Ile Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365 Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380 Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Ser His Thr Pro 385 390 395 400 Ala Asp Ala Glu Arg Ala Gly Leu Leu Val Arg Thr Ser Ala Pro Cys 405 410 415 Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430 Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445 Thr Cys Thr His Pro Phe His His Glu Pro Pro Val Ile Gly Arg Glu 450 455 460 Arg Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr 465 470 475 480 Tyr Val Gln Ser Thr Ala Ala Thr Ala Glu Glu Ile Glu Val His Met 485 490 495 Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Thr Gln Gln Ser Gly Gly 500 505 510 Ser Asn Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys 515 520 525 Asn Cys Gly Gly Ser Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile 530 535 540 Asn Asn Cys Lys Ile Asp Gln Cys His Ala Ala Val Thr Asn His Lys 545 550 555 560 Asn Trp Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly 565 570 575 Asp Arg Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr 580 585 590 Cys Arg Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn 595 600 605 Gln Val Thr Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr 610 615 620 Arg Asn Met Gly Gln Glu Pro Asn Tyr His Glu Glu Trp Val Thr His 625 630 635 640 Lys Lys Glu Val Thr Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr 645 650 655 Trp Gly Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Met Ser Thr Asn 660 665 670 Gly Thr Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu 675 680 685 Leu Tyr Pro Thr Met Thr Val Val Ile Val Ser Val Ala Ser Phe Val 690 695 700 Leu Leu Ser Met Val Gly Thr Ala Val Gly Met Cys Val Cys Ala Arg 705 710 715 720 Arg Arg Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro 725 730 735 Phe Leu Leu Ser Leu Leu Cys Cys Val Arg Thr Thr Lys Ala Ala Thr 740 745 750 Tyr Tyr Glu Ala Ala Ala Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe 755 760 765 Trp Leu Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn 770 775 780 Cys Leu Lys Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala 785 790 795 800 Val Met Ser Ile Gly Ala His Thr Val Ser Ala Tyr Glu His Val Thr 805 810 815 Val Ile Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg 820 825 830 Pro Gly Tyr Ser Pro Met Val Leu Glu Met Glu Leu Gln Ser Val Thr 835 840 845 Leu Glu Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr 850 855 860 Val Ile Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys 865 870 875 880 Asp Lys Ser Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr 885 890 895 Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr 900 905 910 Gln Leu Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu 915 920 925 Phe Ala Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu 930 935 940 Arg Val Leu Tyr Gln Gly Asn Asn Ile Thr Val Ala Ala Tyr Ala Asn 945 950 955 960 Gly Asp His Ala Val Thr Val Lys Asp Ala Lys Phe Val Val Gly Pro 965 970 975 Met Ser Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys 980 985 990 Gly Asp Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro 995 1000 1005 Gly Gln Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp 1010 1015 1020 Val Tyr Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Ala Gly 1025 1030 1035 Thr Val His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr 1040 1045 1050 Trp Leu Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe 1055 1060 1065 Gly Cys Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala 1070 1075 1080 Val Gly Asn Ile Pro Ile Ser Ile Asp Ile Pro Asp Ala Ala Phe 1085 1090 1095 Thr Arg Val Val Asp Ala Pro Ser Val Thr Asp Met Ser Cys Glu 1100 1105 1110 Val Pro Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile 1115 1120 1125 Ile Lys Tyr Thr Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser 1130 1135 1140 Met Thr Asn Ala Val Thr Ile Arg Glu Ala Asp Val Glu Val Glu 1145 1150 1155 Gly Asn Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser 1160 1165 1170 Ala Glu Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala 1175 1180 1185 Ala Ala Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala 1190 1195 1200 Ser His Thr Thr Leu Gly Val Gln Asp Ile Ser Thr Thr Ala Met 1205 1210 1215 Ser Trp Val Gln Lys Ile Thr Gly Gly Val Gly Leu Ile Val Ala 1220 1225 1230 Val Ala Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser 1235 1240 1245 Arg His 1250 <210> 15 <211> 3756 <212> DNA <213> Artificial <220> <223> VLP_CHI 532 vector-CHIKV VLP <400> 15 atggagttca tcccgacgca aactttctat aacagaaggt accaaccccg accctgggcc 60 ccacgcccta caattcaagt aattagacct agaccacgtc cacagaggca ggctgggcaa 120 ctcgcccagc tgatctccgc agtcaacaaa ttgaccatgc gcgcggtacc tcaacagaag 180 cctcgcagaa atcggaaaaa caagaagcaa aggcagaaga agcaggcgcc gcaaaacgac 240 ccaaagcaaa agaagcaacc accacaaaag aagccggctc aaaagaagaa gaaaccaggc 300 cgtagggaga gaatgtgcat gaaaattgaa aatgattgca tcttcgaagt caagcatgaa 360 ggcaaagtga tgggctacgc atgcctggtg ggggataaag taatgaaacc agcacatgtg 420 aagggaacta tcgacaatgc cgatctggct aaactggcct ttaagcggtc gtctaaatac 480 gatcttgaat gtgcacagat accggtgcac atgaagtctg atgcctcgaa gtttacccac 540 gagaaacccg aggggtacta taactggcat cacggagcag tgcagtattc aggaggccgg 600 ttcactatcc cgacgggtgc aggcaagccg ggagacagcg gcagaccgat cttcgacaac 660 aaaggacggg tggtggccat cgtcctagga ggggccaacg aaggtgcccg cacggccctc 720 tccgtggtga cgtggaacaa agacatcgtc acaaaaatta cccctgaggg agccgaagag 780 tggagcctcg ccctcccggt cttgtgcctg ttggcaaaca ctacattccc ctgctctcag 840 ccgccttgca caccctgctg ctacgaaaag gaaccggaaa gcaccttgcg catgcttgag 900 gacaacgtga tgagacccgg atactaccag ctactaaaag catcgctgac ttgctctccc 960 caccgccaaa gacgcagtac taaggacaat tttaatgtct ataaagccac aagaccatat 1020 ctagctcatt gtcctgactg cggagaaggg cattcgtgcc acagccctat cgcattggag 1080 cgcatcagaa atgaagcaac ggacggaacg ctgaaaatcc aggtctcttt gcagatcggg 1140 ataaagacag atgacagcca cgattggacc aagctgcgct atatggatag ccatacgcca 1200 gcggacgcgg agcgagccgg attgcttgta aggacttcag caccgtgcac gatcaccggg 1260 accatgggac actttattct cgcccgatgc ccgaaaggag agacgctgac agtgggattt 1320 acggacagca gaaagatcag ccacacatgc acacacccgt tccatcatga accacctgtg 1380 ataggtaggg agaggttcca ctctcgacca caacatggta aagagttacc ttgcagcacg 1440 tacgtgcaga gcaccgctgc cactgctgag gagatagagg tgcatatgcc cccagatact 1500 cctgaccgca cgctgatgac gcagcagtct ggcaacgtga agatcacagt taatgggcag 1560 acggtgcggt acaagtgcaa ctgcggtggc tccggaagtg gatccaacga gggactgaca 1620 accacagaca aagtgatcaa taactgcaaa attgatcagt gccatgctgc agtcactaat 1680 cacaagaatt ggcaatacaa ctccccttta gtcccgcgca acgctgaact cggggaccgt 1740 aaaggaaaga tccacatccc attcccattg gcaaacgtga cttgcagagt gccaaaagca 1800 agaaacccta cagtaactta cggaaaaaac caagtcacca tgctgctgta tcctgaccat 1860 ccgacactct tgtcttaccg taacatggga caggaaccaa attaccacga ggagtgggtg 1920 acacacaaga aggaggttac cttgaccgtg cctactgagg gtctggaggt cacttggggc 1980 aacaacgaac catacaagta ctggccgcag atgtctacga acggtactgc tcatggtcac 2040 ccacatgaga taatcttgta ctattatgag ctgtacccca ctatgactgt agtcattgtg 2100 tcggtggcct cgttcgtgct tctgtcgatg gtgggcacag cagtgggaat gtgtgtgtgc 2160 gcacggcgca gatgcattac accatatgaa ttaacaccag gagccactgt tcccttcctg 2220 ctcagcctgc tatgctgcgt cagaacgacc aaggcggcca catattacga ggctgcggca 2280 tatctatgga acgaacagca gcccctgttc tggttgcagg ctcttatccc gctggccgcc 2340 ttgatcgtcc tgtgcaactg tctgaaactc ttgccatgct gctgtaagac cctggctttt 2400 ttagccgtaa tgagcatcgg tgcccacact gtgagcgcgt acgaacacgt aacagtgatc 2460 ccgaacacgg tgggagtacc gtataagact cttgtcaaca gaccgggtta cagccccatg 2520 gtgttggaga tggagctaca atcagtcacc ttggaaccaa cactgtcact tgactacatc 2580 acgtgcgagt acaaaactgt catcccctcc ccgtacgtga agtgctgtgg tacagcagag 2640 tgcaaggaca agagcctacc agactacagc tgcaaggtct ttactggagt ctacccattt 2700 atgtggggcg gcgcctactg cttttgcgac gccgaaaata cgcaattgag cgaggcacat 2760 gtagagaaat ctgaatcttg caaaacagag tttgcatcgg cctacagagc ccacaccgca 2820 tcggcgtcgg cgaagctccg cgtcctttac caaggaaaca acattaccgt agctgcctac 2880 gctaacggtg accatgccgt cacagtaaag gacgccaagt ttgtcgtggg cccaatgtcc 2940 tccgcctgga caccttttga caacaaaatc gtggtgtaca aaggcgacgt ctacaacatg 3000 gactacccac cttttggcgc aggaagacca ggacaatttg gtgacattca aagtcgtaca 3060 ccggaaagta aagacgttta tgccaacact cagttggtac tacagaggcc agcagcaggc 3120 acggtacatg taccatactc tcaggcacca tctggcttca agtattggct gaaggaacga 3180 ggagcatcgc tacagcacac ggcaccgttc ggttgccaga ttgcgacaaa cccggtaaga 3240 gctgtaaatt gcgctgtggg gaacatacca atttccatcg acataccgga tgcggccttt 3300 actagggttg tcgatgcacc ctctgtaacg gacatgtcat gcgaagtacc agcctgcact 3360 cactcctccg actttggggg cgtcgccatc atcaaataca cagctagcaa gaaaggtaaa 3420 tgtgcagtac attcgatgac caacgccgtt accattcgag aagccgacgt agaagtagag 3480 gggaactccc agctgcaaat atccttctca acagccctgg caagcgccga gtttcgcgtg 3540 caagtgtgct ccacacaagt acactgcgca gccgcatgcc accctccaaa ggaccacata 3600 gtcaattacc cagcatcaca caccaccctt ggggtccagg atatatccac aacggcaatg 3660 tcttgggtgc agaagattac gggaggagta ggattaattg ttgctgttgc tgccttaatt 3720 ttaattgtgg tgctatgcgt gtcgtttagc aggcac 3756 <210> 16 <211> 1252 <212> PRT <213> Artificial <220> <223> VLP_CHI 532 vector-CHIKV VLP <400> 16 Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro 1 5 10 15 Arg Pro Trp Ala Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30 Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45 Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60 Arg Lys Asn Lys Lys Gln Arg Gln Lys Lys Gln Ala Pro Gln Asn Asp 65 70 75 80 Pro Lys Gln Lys Lys Gln Pro Pro Gln Lys Lys Pro Ala Gln Lys Lys 85 90 95 Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110 Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Met Gly Tyr Ala Cys 115 120 125 Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140 Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr 145 150 155 160 Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175 Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190 Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205 Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220 Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu 225 230 235 240 Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255 Gly Ala Glu Glu Trp Ser Leu Ala Leu Pro Val Leu Cys Leu Leu Ala 260 265 270 Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285 Glu Lys Glu Pro Glu Ser Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300 Arg Pro Gly Tyr Tyr Gln Leu Leu Lys Ala Ser Leu Thr Cys Ser Pro 305 310 315 320 His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335 Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350 Cys His Ser Pro Ile Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365 Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380 Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Ser His Thr Pro 385 390 395 400 Ala Asp Ala Glu Arg Ala Gly Leu Leu Val Arg Thr Ser Ala Pro Cys 405 410 415 Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430 Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445 Thr Cys Thr His Pro Phe His His Glu Pro Pro Val Ile Gly Arg Glu 450 455 460 Arg Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr 465 470 475 480 Tyr Val Gln Ser Thr Ala Ala Thr Ala Glu Glu Ile Glu Val His Met 485 490 495 Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Thr Gln Gln Ser Gly Asn 500 505 510 Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525 Gly Gly Ser Gly Ser Gly Ser Asn Glu Gly Leu Thr Thr Thr Asp Lys 530 535 540 Val Ile Asn Asn Cys Lys Ile Asp Gln Cys His Ala Ala Val Thr Asn 545 550 555 560 His Lys Asn Trp Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn Ala Glu 565 570 575 Leu Gly Asp Arg Lys Gly Lys Ile His Ile Pro Phe Pro Leu Ala Asn 580 585 590 Val Thr Cys Arg Val Pro Lys Ala Arg Asn Pro Thr Val Thr Tyr Gly 595 600 605 Lys Asn Gln Val Thr Met Leu Leu Tyr Pro Asp His Pro Thr Leu Leu 610 615 620 Ser Tyr Arg Asn Met Gly Gln Glu Pro Asn Tyr His Glu Glu Trp Val 625 630 635 640 Thr His Lys Lys Glu Val Thr Leu Thr Val Pro Thr Glu Gly Leu Glu 645 650 655 Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln Met Ser 660 665 670 Thr Asn Gly Thr Ala His Gly His Pro His Glu Ile Ile Leu Tyr Tyr 675 680 685 Tyr Glu Leu Tyr Pro Thr Met Thr Val Val Ile Val Ser Val Ala Ser 690 695 700 Phe Val Leu Leu Ser Met Val Gly Thr Ala Val Gly Met Cys Val Cys 705 710 715 720 Ala Arg Arg Arg Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly Ala Thr 725 730 735 Val Pro Phe Leu Leu Ser Leu Leu Cys Cys Val Arg Thr Thr Lys Ala 740 745 750 Ala Thr Tyr Tyr Glu Ala Ala Ala Tyr Leu Trp Asn Glu Gln Gln Pro 755 760 765 Leu Phe Trp Leu Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile Val Leu 770 775 780 Cys Asn Cys Leu Lys Leu Leu Pro Cys Cys Cys Lys Thr Leu Ala Phe 785 790 795 800 Leu Ala Val Met Ser Ile Gly Ala His Thr Val Ser Ala Tyr Glu His 805 810 815 Val Thr Val Ile Pro Asn Thr Val Gly Val Pro Tyr Lys Thr Leu Val 820 825 830 Asn Arg Pro Gly Tyr Ser Pro Met Val Leu Glu Met Glu Leu Gln Ser 835 840 845 Val Thr Leu Glu Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys Glu Tyr 850 855 860 Lys Thr Val Ile Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr Ala Glu 865 870 875 880 Cys Lys Asp Lys Ser Leu Pro Asp Tyr Ser Cys Lys Val Phe Thr Gly 885 890 895 Val Tyr Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Ala Glu 900 905 910 Asn Thr Gln Leu Ser Glu Ala His Val Glu Lys Ser Glu Ser Cys Lys 915 920 925 Thr Glu Phe Ala Ser Ala Tyr Arg Ala His Thr Ala Ser Ala Ser Ala 930 935 940 Lys Leu Arg Val Leu Tyr Gln Gly Asn Asn Ile Thr Val Ala Ala Tyr 945 950 955 960 Ala Asn Gly Asp His Ala Val Thr Val Lys Asp Ala Lys Phe Val Val 965 970 975 Gly Pro Met Ser Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile Val Val 980 985 990 Tyr Lys Gly Asp Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly 995 1000 1005 Arg Pro Gly Gln Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser 1010 1015 1020 Lys Asp Val Tyr Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala 1025 1030 1035 Ala Gly Thr Val His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe 1040 1045 1050 Lys Tyr Trp Leu Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala 1055 1060 1065 Pro Phe Gly Cys Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn 1070 1075 1080 Cys Ala Val Gly Asn Ile Pro Ile Ser Ile Asp Ile Pro Asp Ala 1085 1090 1095 Ala Phe Thr Arg Val Val Asp Ala Pro Ser Val Thr Asp Met Ser 1100 1105 1110 Cys Glu Val Pro Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val 1115 1120 1125 Ala Ile Ile Lys Tyr Thr Ala Ser Lys Lys Gly Lys Cys Ala Val 1130 1135 1140 His Ser Met Thr Asn Ala Val Thr Ile Arg Glu Ala Asp Val Glu 1145 1150 1155 Val Glu Gly Asn Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu 1160 1165 1170 Ala Ser Ala Glu Phe Arg Val Gln Val Cys Ser Thr Gln Val His 1175 1180 1185 Cys Ala Ala Ala Cys His Pro Pro Lys Asp His Ile Val Asn Tyr 1190 1195 1200 Pro Ala Ser His Thr Thr Leu Gly Val Gln Asp Ile Ser Thr Thr 1205 1210 1215 Ala Met Ser Trp Val Gln Lys Ile Thr Gly Gly Val Gly Leu Ile 1220 1225 1230 Val Ala Val Ala Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser 1235 1240 1245 Phe Ser Arg His 1250 <210> 17 <211> 3777 <212> DNA <213> Artificial <220> <223> VLP_VEEV VLP 518 vector-VEEV VLP <400> 17 atgttcccgt tccagccaat gtatccgatg cagccaatgc cctatcgcaa cccgttcgcg 60 gccccgcgca ggccctggtt ccccagaacc gacccttttc tggcgatgca ggtgcaggaa 120 ttaacccgct cgatggctaa cctgacgttc aagcaacgcc gggacgcgcc acctgagggg 180 ccatccgcta ataaaccgaa gaaggaggcc tcgcaaaaac agaaaggggg aggccaaggg 240 aagaagaaga agaaccaagg gaagaagaag gctaagacag ggccgcctaa tccgaaggca 300 cagaatggaa acaagaagaa gaccaacaag aaaccaggca agagacagcg catggtcatg 360 aaattggaat ctgacaagac gttcccaatc atgttggaag ggaagataaa cggctacgct 420 tgtgtggtcg gagggaagtt attcaggccg atgcatgtgg aaggcaagat cgacaacgac 480 gttctggccg cgcttaagac gaagaaagca tccaaatacg atcttgagta tgcagatgtg 540 ccacagaaca tgcgggccga tacattcaaa tacacccatg agaaacccca aggctattac 600 agctggcatc atggagcagt ccaatatgaa aatgggcgtt tcacggtgcc gaaaggagtt 660 ggggccaagg gagacagcgg acgacccatt ctggataacc agggacgggt ggtcgctatt 720 gtgctgggag gtgtgaatga aggatctagg acagcccttt cagtcgtcat gtggaacgag 780 aagggagtta ccgtgaagta tactccagag aactgcgagc aatggtcact agtgaccacc 840 atgtgtctgc tcgccaatgt gacgttccca tgtgctcaac caccaatttg ctacgacaga 900 aaaccagcag agactttggc catgctcagc gttaacgttg acaacccggg ctacgatgag 960 ctgctggaag cagctgttaa gtgccccgga aggaaaagga gatccaccga ggagctgttt 1020 aatgagtata agctaacgcg cccttacatg gccagatgca tcagatgtgc agttgggagc 1080 tgccatagtc caatagcaat cgaggcagta aagagcgacg ggcacgacgg ttatgttaga 1140 cttcagactt cctcgcagta tggcctggat tcctccggca acttaaaggg caggaccatg 1200 cggtatgaca tgcacgggac cattaaagag ataccactac atcaagtgtc actctataca 1260 tctcgcccgt gtcacattgt ggatgggcac ggttatttcc tgcttgccag gtgcccggca 1320 ggggactcca tcaccatgga atttaagaaa gattccgtca gacactcctg ctcggtgccg 1380 tatgaagtga aatttaatcc tgtaggcaga gaactctata ctcatccccc agaacacgga 1440 gtagagcaag cgtgccaagt ctacgcacat gatgcacaga acagaggagc ttatgtcgag 1500 atgcacctcc cgggctcaga agtggacagc agtttggttt ccttgagcgg ctccggagga 1560 tccagttcag tcaccgtgac acctcctgat gggactagcg ccctggtgga atgcgagtgt 1620 ggcggcacaa agatctccga gaccatcaac aagacaaaac agttcagcca gtgcacaaag 1680 aaggagcagt gcagagcata tcggctgcag aacgataagt gggtgtataa ttctgacaaa 1740 ctgcccaaag cagcgggagc caccttaaaa ggaaaactgc atgtcccatt cttgctggca 1800 gacggcaaat gcaccgtgcc tctagcacca gaacctatga taaccttcgg tttcagatca 1860 gtgtcactga aactgcaccc taagaatccc acatatctaa tcacccgcca acttgctgat 1920 gagcctcact acacgcacga gctcatatct gaaccagctg ttaggaattt taccgtcacc 1980 gaaaaagggt gggagtttgt atggggaaac cacccgccga aaaggttttg ggcacaggaa 2040 acagcacccg gaaatccaca tgggctaccg cacgaggtga taactcatta ttaccacaga 2100 taccctatgt ccaccatcct gggtttgtca atttgtgccg ccattgcaac cgtttccgtt 2160 gcagcgtcta cctggctgtt ttgcagatca agagttgcgt gcctaactcc ttaccggcta 2220 acacctaacg ctaggatacc attttgtctg gctgtgcttt gctgcgcccg cactgcccgg 2280 gccgagacca cctgggagtc cttggatcac ctatggaaca ataaccaaca gatgttctgg 2340 attcaattgc tgatccctct ggccgccttg atcgtagtga ctcgcctgct caggtgcgtg 2400 tgctgtgtcg tgcctttttt agtcatggcc ggcgccgcag gcgccggcgc ctacgagcac 2460 gcgaccacga tgccgagcca agcgggaatc tcgtataaca ctatagtcaa cagagcaggc 2520 tacgcaccac tccctatcag cataacacca acaaagatca agctgatacc tacagtgaac 2580 ttggagtacg tcacctgcca ctacaaaaca ggaatggatt caccagccat caaatgctgc 2640 ggatctcagg aatgcactcc aacttacagg cctgatgaac agtgcaaagt cttcacaggg 2700 gtttacccgt tcatgtgggg tggtgcatat tgcttttgcg acactgagaa cacccaagtc 2760 agcaaggcct acgtaatgaa atctgacgac tgccttgcgg atcatgctga agcatataaa 2820 gcgcacacag cctcagtgca ggcgttcctc aacatcacag tgggagaaca ctctattgtg 2880 actaccgtgt atgtgaatgg agaaactcct gtgaatttca atggggtcaa aataactgca 2940 ggtccgcttt ccacagcttg gacacccttt gatcgcaaaa tcgtgcagta tgccggggag 3000 atctataatt atgattttcc tgagtatggg gcaggacaac caggagcatt tggagatata 3060 caatccagaa cagtctcaag ctctgatctg tatgccaata ccaacctagt gctgcagaga 3120 cccaaagcag gagcgatcca cgtgccatac actcaggcac cttcgggttt tgagcaatgg 3180 aagaaagata aagctccatc attgaaattt accgcccctt tcggatgcga aatatataca 3240 aaccccattc gcgccgaaaa ctgtgctgta gggtcaattc cattagcctt tgacattccc 3300 gacgccttgt tcaccagggt gtcagaaaca ccgacacttt cagcggccga atgcactctt 3360 aacgagtgcg tgtattcttc cgactttggt gggatcgcca cggtcaagta ctcggccagc 3420 aagtcaggca agtgcgcagt ccatgtgcca tcagggactg ctaccctaaa agaagcagca 3480 gtcgagctaa ccgagcaagg gtcggcgact atccatttct cgaccgcaaa tatccacccg 3540 gagttcaggc tccaaatatg cacatcatat gttacgtgca aaggtgattg tcaccccccg 3600 aaagaccata ttgtgacaca ccctcagtat cacgcccaaa catttacagc cgcggtgtca 3660 aaaaccgcgt ggacgtggtt aacatccctg ctgggaggat cagccgtaat tattataatt 3720 ggcttggtgc tggctactat tgtggccatg tacgtgctga ccaaccagaa acataat 3777 <210> 18 <211> 1259 <212> PRT <213> Artificial <220> <223> VLP_VEEV VLP 518 vector-VEEV VLP <400> 18 Met Phe Pro Phe Gln Pro Met Tyr Pro Met Gln Pro Met Pro Tyr Arg 1 5 10 15 Asn Pro Phe Ala Ala Pro Arg Arg Pro Trp Phe Pro Arg Thr Asp Pro 20 25 30 Phe Leu Ala Met Gln Val Gln Glu Leu Thr Arg Ser Met Ala Asn Leu 35 40 45 Thr Phe Lys Gln Arg Arg Asp Ala Pro Pro Glu Gly Pro Ser Ala Asn 50 55 60 Lys Pro Lys Lys Glu Ala Ser Gln Lys Gln Lys Gly Gly Gly Gln Gly 65 70 75 80 Lys Lys Lys Lys Asn Gln Gly Lys Lys Lys Ala Lys Thr Gly Pro Pro 85 90 95 Asn Pro Lys Ala Gln Asn Gly Asn Lys Lys Lys Thr Asn Lys Lys Pro 100 105 110 Gly Lys Arg Gln Arg Met Val Met Lys Leu Glu Ser Asp Lys Thr Phe 115 120 125 Pro Ile Met Leu Glu Gly Lys Ile Asn Gly Tyr Ala Cys Val Val Gly 130 135 140 Gly Lys Leu Phe Arg Pro Met His Val Glu Gly Lys Ile Asp Asn Asp 145 150 155 160 Val Leu Ala Ala Leu Lys Thr Lys Lys Ala Ser Lys Tyr Asp Leu Glu 165 170 175 Tyr Ala Asp Val Pro Gln Asn Met Arg Ala Asp Thr Phe Lys Tyr Thr 180 185 190 His Glu Lys Pro Gln Gly Tyr Tyr Ser Trp His His Gly Ala Val Gln 195 200 205 Tyr Glu Asn Gly Arg Phe Thr Val Pro Lys Gly Val Gly Ala Lys Gly 210 215 220 Asp Ser Gly Arg Pro Ile Leu Asp Asn Gln Gly Arg Val Val Ala Ile 225 230 235 240 Val Leu Gly Gly Val Asn Glu Gly Ser Arg Thr Ala Leu Ser Val Val 245 250 255 Met Trp Asn Glu Lys Gly Val Thr Val Lys Tyr Thr Pro Glu Asn Cys 260 265 270 Glu Gln Trp Ser Leu Val Thr Thr Met Cys Leu Leu Ala Asn Val Thr 275 280 285 Phe Pro Cys Ala Gln Pro Pro Ile Cys Tyr Asp Arg Lys Pro Ala Glu 290 295 300 Thr Leu Ala Met Leu Ser Val Asn Val Asp Asn Pro Gly Tyr Asp Glu 305 310 315 320 Leu Leu Glu Ala Ala Val Lys Cys Pro Gly Arg Lys Arg Arg Ser Thr 325 330 335 Glu Glu Leu Phe Asn Glu Tyr Lys Leu Thr Arg Pro Tyr Met Ala Arg 340 345 350 Cys Ile Arg Cys Ala Val Gly Ser Cys His Ser Pro Ile Ala Ile Glu 355 360 365 Ala Val Lys Ser Asp Gly His Asp Gly Tyr Val Arg Leu Gln Thr Ser 370 375 380 Ser Gln Tyr Gly Leu Asp Ser Ser Gly Asn Leu Lys Gly Arg Thr Met 385 390 395 400 Arg Tyr Asp Met His Gly Thr Ile Lys Glu Ile Pro Leu His Gln Val 405 410 415 Ser Leu Tyr Thr Ser Arg Pro Cys His Ile Val Asp Gly His Gly Tyr 420 425 430 Phe Leu Leu Ala Arg Cys Pro Ala Gly Asp Ser Ile Thr Met Glu Phe 435 440 445 Lys Lys Asp Ser Val Arg His Ser Cys Ser Val Pro Tyr Glu Val Lys 450 455 460 Phe Asn Pro Val Gly Arg Glu Leu Tyr Thr His Pro Pro Glu His Gly 465 470 475 480 Val Glu Gln Ala Cys Gln Val Tyr Ala His Asp Ala Gln Asn Arg Gly 485 490 495 Ala Tyr Val Glu Met His Leu Pro Gly Ser Glu Val Asp Ser Ser Leu 500 505 510 Val Ser Leu Ser Gly Ser Gly Gly Ser Ser Ser Val Thr Val Thr Pro 515 520 525 Pro Asp Gly Thr Ser Ala Leu Val Glu Cys Glu Cys Gly Gly Thr Lys 530 535 540 Ile Ser Glu Thr Ile Asn Lys Thr Lys Gln Phe Ser Gln Cys Thr Lys 545 550 555 560 Lys Glu Gln Cys Arg Ala Tyr Arg Leu Gln Asn Asp Lys Trp Val Tyr 565 570 575 Asn Ser Asp Lys Leu Pro Lys Ala Ala Gly Ala Thr Leu Lys Gly Lys 580 585 590 Leu His Val Pro Phe Leu Leu Ala Asp Gly Lys Cys Thr Val Pro Leu 595 600 605 Ala Pro Glu Pro Met Ile Thr Phe Gly Phe Arg Ser Val Ser Leu Lys 610 615 620 Leu His Pro Lys Asn Pro Thr Tyr Leu Ile Thr Arg Gln Leu Ala Asp 625 630 635 640 Glu Pro His Tyr Thr His Glu Leu Ile Ser Glu Pro Ala Val Arg Asn 645 650 655 Phe Thr Val Thr Glu Lys Gly Trp Glu Phe Val Trp Gly Asn His Pro 660 665 670 Pro Lys Arg Phe Trp Ala Gln Glu Thr Ala Pro Gly Asn Pro His Gly 675 680 685 Leu Pro His Glu Val Ile Thr His Tyr Tyr His Arg Tyr Pro Met Ser 690 695 700 Thr Ile Leu Gly Leu Ser Ile Cys Ala Ala Ile Ala Thr Val Ser Val 705 710 715 720 Ala Ala Ser Thr Trp Leu Phe Cys Arg Ser Arg Val Ala Cys Leu Thr 725 730 735 Pro Tyr Arg Leu Thr Pro Asn Ala Arg Ile Pro Phe Cys Leu Ala Val 740 745 750 Leu Cys Cys Ala Arg Thr Ala Arg Ala Glu Thr Thr Trp Glu Ser Leu 755 760 765 Asp His Leu Trp Asn Asn Asn Gln Gln Met Phe Trp Ile Gln Leu Leu 770 775 780 Ile Pro Leu Ala Ala Leu Ile Val Val Thr Arg Leu Leu Arg Cys Val 785 790 795 800 Cys Cys Val Val Pro Phe Leu Val Met Ala Gly Ala Ala Gly Ala Gly 805 810 815 Ala Tyr Glu His Ala Thr Thr Met Pro Ser Gln Ala Gly Ile Ser Tyr 820 825 830 Asn Thr Ile Val Asn Arg Ala Gly Tyr Ala Pro Leu Pro Ile Ser Ile 835 840 845 Thr Pro Thr Lys Ile Lys Leu Ile Pro Thr Val Asn Leu Glu Tyr Val 850 855 860 Thr Cys His Tyr Lys Thr Gly Met Asp Ser Pro Ala Ile Lys Cys Cys 865 870 875 880 Gly Ser Gln Glu Cys Thr Pro Thr Tyr Arg Pro Asp Glu Gln Cys Lys 885 890 895 Val Phe Thr Gly Val Tyr Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe 900 905 910 Cys Asp Thr Glu Asn Thr Gln Val Ser Lys Ala Tyr Val Met Lys Ser 915 920 925 Asp Asp Cys Leu Ala Asp His Ala Glu Ala Tyr Lys Ala His Thr Ala 930 935 940 Ser Val Gln Ala Phe Leu Asn Ile Thr Val Gly Glu His Ser Ile Val 945 950 955 960 Thr Thr Val Tyr Val Asn Gly Glu Thr Pro Val Asn Phe Asn Gly Val 965 970 975 Lys Ile Thr Ala Gly Pro Leu Ser Thr Ala Trp Thr Pro Phe Asp Arg 980 985 990 Lys Ile Val Gln Tyr Ala Gly Glu Ile Tyr Asn Tyr Asp Phe Pro Glu 995 1000 1005 Tyr Gly Ala Gly Gln Pro Gly Ala Phe Gly Asp Ile Gln Ser Arg 1010 1015 1020 Thr Val Ser Ser Ser Asp Leu Tyr Ala Asn Thr Asn Leu Val Leu 1025 1030 1035 Gln Arg Pro Lys Ala Gly Ala Ile His Val Pro Tyr Thr Gln Ala 1040 1045 1050 Pro Ser Gly Phe Glu Gln Trp Lys Lys Asp Lys Ala Pro Ser Leu 1055 1060 1065 Lys Phe Thr Ala Pro Phe Gly Cys Glu Ile Tyr Thr Asn Pro Ile 1070 1075 1080 Arg Ala Glu Asn Cys Ala Val Gly Ser Ile Pro Leu Ala Phe Asp 1085 1090 1095 Ile Pro Asp Ala Leu Phe Thr Arg Val Ser Glu Thr Pro Thr Leu 1100 1105 1110 Ser Ala Ala Glu Cys Thr Leu Asn Glu Cys Val Tyr Ser Ser Asp 1115 1120 1125 Phe Gly Gly Ile Ala Thr Val Lys Tyr Ser Ala Ser Lys Ser Gly 1130 1135 1140 Lys Cys Ala Val His Val Pro Ser Gly Thr Ala Thr Leu Lys Glu 1145 1150 1155 Ala Ala Val Glu Leu Thr Glu Gln Gly Ser Ala Thr Ile His Phe 1160 1165 1170 Ser Thr Ala Asn Ile His Pro Glu Phe Arg Leu Gln Ile Cys Thr 1175 1180 1185 Ser Tyr Val Thr Cys Lys Gly Asp Cys His Pro Pro Lys Asp His 1190 1195 1200 Ile Val Thr His Pro Gln Tyr His Ala Gln Thr Phe Thr Ala Ala 1205 1210 1215 Val Ser Lys Thr Ala Trp Thr Trp Leu Thr Ser Leu Leu Gly Gly 1220 1225 1230 Ser Ala Val Ile Ile Ile Ile Gly Leu Val Leu Ala Thr Ile Val 1235 1240 1245 Ala Met Tyr Val Leu Thr Asn Gln Lys His Asn 1250 1255 <210> 19 <211> 3777 <212> DNA <213> Artificial <220> <223> VLP_VEEV VLP 519 vector-VEEV VLP <400> 19 atgttcccgt tccagccaat gtatccgatg cagccaatgc cctatcgcaa cccgttcgcg 60 gccccgcgca ggccctggtt ccccagaacc gacccttttc tggcgatgca ggtgcaggaa 120 ttaacccgct cgatggctaa cctgacgttc aagcaacgcc gggacgcgcc acctgagggg 180 ccatccgcta ataaaccgaa gaaggaggcc tcgcaaaaac agaaaggggg aggccaaggg 240 aagaagaaga agaaccaagg gaagaagaag gctaagacag ggccgcctaa tccgaaggca 300 cagaatggaa acaagaagaa gaccaacaag aaaccaggca agagacagcg catggtcatg 360 aaattggaat ctgacaagac gttcccaatc atgttggaag ggaagataaa cggctacgct 420 tgtgtggtcg gagggaagtt attcaggccg atgcatgtgg aaggcaagat cgacaacgac 480 gttctggccg cgcttaagac gaagaaagca tccaaatacg atcttgagta tgcagatgtg 540 ccacagaaca tgcgggccga tacattcaaa tacacccatg agaaacccca aggctattac 600 agctggcatc atggagcagt ccaatatgaa aatgggcgtt tcacggtgcc gaaaggagtt 660 ggggccaagg gagacagcgg acgacccatt ctggataacc agggacgggt ggtcgctatt 720 gtgctgggag gtgtgaatga aggatctagg acagcccttt cagtcgtcat gtggaacgag 780 aagggagtta ccgtgaagta tactccagag aactgcgagc aatggtcact agtgaccacc 840 atgtgtctgc tcgccaatgt gacgttccca tgtgctcaac caccaatttg ctacgacaga 900 aaaccagcag agactttggc catgctcagc gttaacgttg acaacccggg ctacgatgag 960 ctgctggaag cagctgttaa gtgccccgga aggaaaagga gatccaccga ggagctgttt 1020 aatgagtata agctaacgcg cccttacatg gccagatgca tcagatgtgc agttgggagc 1080 tgccatagtc caatagcaat cgaggcagta aagagcgacg ggcacgacgg ttatgttaga 1140 cttcagactt cctcgcagta tggcctggat tcctccggca acttaaaggg caggaccatg 1200 cggtatgaca tgcacgggac cattaaagag ataccactac atcaagtgtc actctataca 1260 tctcgcccgt gtcacattgt ggatgggcac ggttatttcc tgcttgccag gtgcccggca 1320 ggggactcca tcaccatgga atttaagaaa gattccgtca gacactcctg ctcggtgccg 1380 tatgaagtga aatttaatcc tgtaggcaga gaactctata ctcatccccc agaacacgga 1440 gtagagcaag cgtgccaagt ctacgcacat gatgcacaga acagaggagc ttatgtcgag 1500 atgcacctcc cgggctcaga agtggacagc agtttggttt ccttgagcgg cagttccgga 1560 ggatcctcag tcaccgtgac acctcctgat gggactagcg ccctggtgga atgcgagtgt 1620 ggcggcacaa agatctccga gaccatcaac aagacaaaac agttcagcca gtgcacaaag 1680 aaggagcagt gcagagcata tcggctgcag aacgataagt gggtgtataa ttctgacaaa 1740 ctgcccaaag cagcgggagc caccttaaaa ggaaaactgc atgtcccatt cttgctggca 1800 gacggcaaat gcaccgtgcc tctagcacca gaacctatga taaccttcgg tttcagatca 1860 gtgtcactga aactgcaccc taagaatccc acatatctaa tcacccgcca acttgctgat 1920 gagcctcact acacgcacga gctcatatct gaaccagctg ttaggaattt taccgtcacc 1980 gaaaaagggt gggagtttgt atggggaaac cacccgccga aaaggttttg ggcacaggaa 2040 acagcacccg gaaatccaca tgggctaccg cacgaggtga taactcatta ttaccacaga 2100 taccctatgt ccaccatcct gggtttgtca atttgtgccg ccattgcaac cgtttccgtt 2160 gcagcgtcta cctggctgtt ttgcagatca agagttgcgt gcctaactcc ttaccggcta 2220 acacctaacg ctaggatacc attttgtctg gctgtgcttt gctgcgcccg cactgcccgg 2280 gccgagacca cctgggagtc cttggatcac ctatggaaca ataaccaaca gatgttctgg 2340 attcaattgc tgatccctct ggccgccttg atcgtagtga ctcgcctgct caggtgcgtg 2400 tgctgtgtcg tgcctttttt agtcatggcc ggcgccgcag gcgccggcgc ctacgagcac 2460 gcgaccacga tgccgagcca agcgggaatc tcgtataaca ctatagtcaa cagagcaggc 2520 tacgcaccac tccctatcag cataacacca acaaagatca agctgatacc tacagtgaac 2580 ttggagtacg tcacctgcca ctacaaaaca ggaatggatt caccagccat caaatgctgc 2640 ggatctcagg aatgcactcc aacttacagg cctgatgaac agtgcaaagt cttcacaggg 2700 gtttacccgt tcatgtgggg tggtgcatat tgcttttgcg acactgagaa cacccaagtc 2760 agcaaggcct acgtaatgaa atctgacgac tgccttgcgg atcatgctga agcatataaa 2820 gcgcacacag cctcagtgca ggcgttcctc aacatcacag tgggagaaca ctctattgtg 2880 actaccgtgt atgtgaatgg agaaactcct gtgaatttca atggggtcaa aataactgca 2940 ggtccgcttt ccacagcttg gacacccttt gatcgcaaaa tcgtgcagta tgccggggag 3000 atctataatt atgattttcc tgagtatggg gcaggacaac caggagcatt tggagatata 3060 caatccagaa cagtctcaag ctctgatctg tatgccaata ccaacctagt gctgcagaga 3120 cccaaagcag gagcgatcca cgtgccatac actcaggcac cttcgggttt tgagcaatgg 3180 aagaaagata aagctccatc attgaaattt accgcccctt tcggatgcga aatatataca 3240 aaccccattc gcgccgaaaa ctgtgctgta gggtcaattc cattagcctt tgacattccc 3300 gacgccttgt tcaccagggt gtcagaaaca ccgacacttt cagcggccga atgcactctt 3360 aacgagtgcg tgtattcttc cgactttggt gggatcgcca cggtcaagta ctcggccagc 3420 aagtcaggca agtgcgcagt ccatgtgcca tcagggactg ctaccctaaa agaagcagca 3480 gtcgagctaa ccgagcaagg gtcggcgact atccatttct cgaccgcaaa tatccacccg 3540 gagttcaggc tccaaatatg cacatcatat gttacgtgca aaggtgattg tcaccccccg 3600 aaagaccata ttgtgacaca ccctcagtat cacgcccaaa catttacagc cgcggtgtca 3660 aaaaccgcgt ggacgtggtt aacatccctg ctgggaggat cagccgtaat tattataatt 3720 ggcttggtgc tggctactat tgtggccatg tacgtgctga ccaaccagaa acataat 3777 <210> 20 <211> 1259 <212> PRT <213> Artificial <220> <223> VLP_VEEV VLP 519 vector-VEEV VLP <400> 20 Met Phe Pro Phe Gln Pro Met Tyr Pro Met Gln Pro Met Pro Tyr Arg 1 5 10 15 Asn Pro Phe Ala Ala Pro Arg Arg Pro Trp Phe Pro Arg Thr Asp Pro 20 25 30 Phe Leu Ala Met Gln Val Gln Glu Leu Thr Arg Ser Met Ala Asn Leu 35 40 45 Thr Phe Lys Gln Arg Arg Asp Ala Pro Pro Glu Gly Pro Ser Ala Asn 50 55 60 Lys Pro Lys Lys Glu Ala Ser Gln Lys Gln Lys Gly Gly Gly Gln Gly 65 70 75 80 Lys Lys Lys Lys Asn Gln Gly Lys Lys Lys Ala Lys Thr Gly Pro Pro 85 90 95 Asn Pro Lys Ala Gln Asn Gly Asn Lys Lys Lys Thr Asn Lys Lys Pro 100 105 110 Gly Lys Arg Gln Arg Met Val Met Lys Leu Glu Ser Asp Lys Thr Phe 115 120 125 Pro Ile Met Leu Glu Gly Lys Ile Asn Gly Tyr Ala Cys Val Val Gly 130 135 140 Gly Lys Leu Phe Arg Pro Met His Val Glu Gly Lys Ile Asp Asn Asp 145 150 155 160 Val Leu Ala Ala Leu Lys Thr Lys Lys Ala Ser Lys Tyr Asp Leu Glu 165 170 175 Tyr Ala Asp Val Pro Gln Asn Met Arg Ala Asp Thr Phe Lys Tyr Thr 180 185 190 His Glu Lys Pro Gln Gly Tyr Tyr Ser Trp His His Gly Ala Val Gln 195 200 205 Tyr Glu Asn Gly Arg Phe Thr Val Pro Lys Gly Val Gly Ala Lys Gly 210 215 220 Asp Ser Gly Arg Pro Ile Leu Asp Asn Gln Gly Arg Val Val Ala Ile 225 230 235 240 Val Leu Gly Gly Val Asn Glu Gly Ser Arg Thr Ala Leu Ser Val Val 245 250 255 Met Trp Asn Glu Lys Gly Val Thr Val Lys Tyr Thr Pro Glu Asn Cys 260 265 270 Glu Gln Trp Ser Leu Val Thr Thr Met Cys Leu Leu Ala Asn Val Thr 275 280 285 Phe Pro Cys Ala Gln Pro Pro Ile Cys Tyr Asp Arg Lys Pro Ala Glu 290 295 300 Thr Leu Ala Met Leu Ser Val Asn Val Asp Asn Pro Gly Tyr Asp Glu 305 310 315 320 Leu Leu Glu Ala Ala Val Lys Cys Pro Gly Arg Lys Arg Arg Ser Thr 325 330 335 Glu Glu Leu Phe Asn Glu Tyr Lys Leu Thr Arg Pro Tyr Met Ala Arg 340 345 350 Cys Ile Arg Cys Ala Val Gly Ser Cys His Ser Pro Ile Ala Ile Glu 355 360 365 Ala Val Lys Ser Asp Gly His Asp Gly Tyr Val Arg Leu Gln Thr Ser 370 375 380 Ser Gln Tyr Gly Leu Asp Ser Ser Gly Asn Leu Lys Gly Arg Thr Met 385 390 395 400 Arg Tyr Asp Met His Gly Thr Ile Lys Glu Ile Pro Leu His Gln Val 405 410 415 Ser Leu Tyr Thr Ser Arg Pro Cys His Ile Val Asp Gly His Gly Tyr 420 425 430 Phe Leu Leu Ala Arg Cys Pro Ala Gly Asp Ser Ile Thr Met Glu Phe 435 440 445 Lys Lys Asp Ser Val Arg His Ser Cys Ser Val Pro Tyr Glu Val Lys 450 455 460 Phe Asn Pro Val Gly Arg Glu Leu Tyr Thr His Pro Pro Glu His Gly 465 470 475 480 Val Glu Gln Ala Cys Gln Val Tyr Ala His Asp Ala Gln Asn Arg Gly 485 490 495 Ala Tyr Val Glu Met His Leu Pro Gly Ser Glu Val Asp Ser Ser Leu 500 505 510 Val Ser Leu Ser Gly Ser Ser Gly Gly Ser Ser Val Thr Val Thr Pro 515 520 525 Pro Asp Gly Thr Ser Ala Leu Val Glu Cys Glu Cys Gly Gly Thr Lys 530 535 540 Ile Ser Glu Thr Ile Asn Lys Thr Lys Gln Phe Ser Gln Cys Thr Lys 545 550 555 560 Lys Glu Gln Cys Arg Ala Tyr Arg Leu Gln Asn Asp Lys Trp Val Tyr 565 570 575 Asn Ser Asp Lys Leu Pro Lys Ala Ala Gly Ala Thr Leu Lys Gly Lys 580 585 590 Leu His Val Pro Phe Leu Leu Ala Asp Gly Lys Cys Thr Val Pro Leu 595 600 605 Ala Pro Glu Pro Met Ile Thr Phe Gly Phe Arg Ser Val Ser Leu Lys 610 615 620 Leu His Pro Lys Asn Pro Thr Tyr Leu Ile Thr Arg Gln Leu Ala Asp 625 630 635 640 Glu Pro His Tyr Thr His Glu Leu Ile Ser Glu Pro Ala Val Arg Asn 645 650 655 Phe Thr Val Thr Glu Lys Gly Trp Glu Phe Val Trp Gly Asn His Pro 660 665 670 Pro Lys Arg Phe Trp Ala Gln Glu Thr Ala Pro Gly Asn Pro His Gly 675 680 685 Leu Pro His Glu Val Ile Thr His Tyr Tyr His Arg Tyr Pro Met Ser 690 695 700 Thr Ile Leu Gly Leu Ser Ile Cys Ala Ala Ile Ala Thr Val Ser Val 705 710 715 720 Ala Ala Ser Thr Trp Leu Phe Cys Arg Ser Arg Val Ala Cys Leu Thr 725 730 735 Pro Tyr Arg Leu Thr Pro Asn Ala Arg Ile Pro Phe Cys Leu Ala Val 740 745 750 Leu Cys Cys Ala Arg Thr Ala Arg Ala Glu Thr Thr Trp Glu Ser Leu 755 760 765 Asp His Leu Trp Asn Asn Asn Gln Gln Met Phe Trp Ile Gln Leu Leu 770 775 780 Ile Pro Leu Ala Ala Leu Ile Val Val Thr Arg Leu Leu Arg Cys Val 785 790 795 800 Cys Cys Val Val Pro Phe Leu Val Met Ala Gly Ala Ala Gly Ala Gly 805 810 815 Ala Tyr Glu His Ala Thr Thr Met Pro Ser Gln Ala Gly Ile Ser Tyr 820 825 830 Asn Thr Ile Val Asn Arg Ala Gly Tyr Ala Pro Leu Pro Ile Ser Ile 835 840 845 Thr Pro Thr Lys Ile Lys Leu Ile Pro Thr Val Asn Leu Glu Tyr Val 850 855 860 Thr Cys His Tyr Lys Thr Gly Met Asp Ser Pro Ala Ile Lys Cys Cys 865 870 875 880 Gly Ser Gln Glu Cys Thr Pro Thr Tyr Arg Pro Asp Glu Gln Cys Lys 885 890 895 Val Phe Thr Gly Val Tyr Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe 900 905 910 Cys Asp Thr Glu Asn Thr Gln Val Ser Lys Ala Tyr Val Met Lys Ser 915 920 925 Asp Asp Cys Leu Ala Asp His Ala Glu Ala Tyr Lys Ala His Thr Ala 930 935 940 Ser Val Gln Ala Phe Leu Asn Ile Thr Val Gly Glu His Ser Ile Val 945 950 955 960 Thr Thr Val Tyr Val Asn Gly Glu Thr Pro Val Asn Phe Asn Gly Val 965 970 975 Lys Ile Thr Ala Gly Pro Leu Ser Thr Ala Trp Thr Pro Phe Asp Arg 980 985 990 Lys Ile Val Gln Tyr Ala Gly Glu Ile Tyr Asn Tyr Asp Phe Pro Glu 995 1000 1005 Tyr Gly Ala Gly Gln Pro Gly Ala Phe Gly Asp Ile Gln Ser Arg 1010 1015 1020 Thr Val Ser Ser Ser Asp Leu Tyr Ala Asn Thr Asn Leu Val Leu 1025 1030 1035 Gln Arg Pro Lys Ala Gly Ala Ile His Val Pro Tyr Thr Gln Ala 1040 1045 1050 Pro Ser Gly Phe Glu Gln Trp Lys Lys Asp Lys Ala Pro Ser Leu 1055 1060 1065 Lys Phe Thr Ala Pro Phe Gly Cys Glu Ile Tyr Thr Asn Pro Ile 1070 1075 1080 Arg Ala Glu Asn Cys Ala Val Gly Ser Ile Pro Leu Ala Phe Asp 1085 1090 1095 Ile Pro Asp Ala Leu Phe Thr Arg Val Ser Glu Thr Pro Thr Leu 1100 1105 1110 Ser Ala Ala Glu Cys Thr Leu Asn Glu Cys Val Tyr Ser Ser Asp 1115 1120 1125 Phe Gly Gly Ile Ala Thr Val Lys Tyr Ser Ala Ser Lys Ser Gly 1130 1135 1140 Lys Cys Ala Val His Val Pro Ser Gly Thr Ala Thr Leu Lys Glu 1145 1150 1155 Ala Ala Val Glu Leu Thr Glu Gln Gly Ser Ala Thr Ile His Phe 1160 1165 1170 Ser Thr Ala Asn Ile His Pro Glu Phe Arg Leu Gln Ile Cys Thr 1175 1180 1185 Ser Tyr Val Thr Cys Lys Gly Asp Cys His Pro Pro Lys Asp His 1190 1195 1200 Ile Val Thr His Pro Gln Tyr His Ala Gln Thr Phe Thr Ala Ala 1205 1210 1215 Val Ser Lys Thr Ala Trp Thr Trp Leu Thr Ser Leu Leu Gly Gly 1220 1225 1230 Ser Ala Val Ile Ile Ile Ile Gly Leu Val Leu Ala Thr Ile Val 1235 1240 1245 Ala Met Tyr Val Leu Thr Asn Gln Lys His Asn 1250 1255 <210> 21 <211> 3777 <212> DNA <213> Artificial <220> <223> VLP_VEEV VLP 538 vector-VEEV VLP <400> 21 atgttcccgt tccagccaat gtatccgatg cagccaatgc cctatcgcaa cccgttcgcg 60 gccccgcgca ggccctggtt ccccagaacc gacccttttc tggcgatgca ggtgcaggaa 120 ttaacccgct cgatggctaa cctgacgttc aagcaacgcc gggacgcgcc acctgagggg 180 ccatccgcta ataaaccgaa gaaggaggcc tcgcaaaaac agaaaggggg aggccaaggg 240 aagaagaaga agaaccaagg gaagaagaag gctaagacag ggccgcctaa tccgaaggca 300 cagaatggaa acaagaagaa gaccaacaag aaaccaggca agagacagcg catggtcatg 360 aaattggaat ctgacaagac gttcccaatc atgttggaag ggaagataaa cggctacgct 420 tgtgtggtcg gagggaagtt attcaggccg atgcatgtgg aaggcaagat cgacaacgac 480 gttctggccg cgcttaagac gaagaaagca tccaaatacg atcttgagta tgcagatgtg 540 ccacagaaca tgcgggccga tacattcaaa tacacccatg agaaacccca aggctattac 600 agctggcatc atggagcagt ccaatatgaa aatgggcgtt tcacggtgcc gaaaggagtt 660 ggggccaagg gagacagcgg acgacccatt ctggataacc agggacgggt ggtcgctatt 720 gtgctgggag gtgtgaatga aggatctagg acagcccttt cagtcgtcat gtggaacgag 780 aagggagtta ccgtgaagta tactccagag aactgcgagc aatggtcact agtgaccacc 840 atgtgtctgc tcgccaatgt gacgttccca tgtgctcaac caccaatttg ctacgacaga 900 aaaccagcag agactttggc catgctcagc gttaacgttg acaacccggg ctacgatgag 960 ctgctggaag cagctgttaa gtgccccgga aggaaaagga gatccaccga ggagctgttt 1020 aatgagtata agctaacgcg cccttacatg gccagatgca tcagatgtgc agttgggagc 1080 tgccatagtc caatagcaat cgaggcagta aagagcgacg ggcacgacgg ttatgttaga 1140 cttcagactt cctcgcagta tggcctggat tcctccggca acttaaaggg caggaccatg 1200 cggtatgaca tgcacgggac cattaaagag ataccactac atcaagtgtc actctataca 1260 tctcgcccgt gtcacattgt ggatgggcac ggttatttcc tgcttgccag gtgcccggca 1320 ggggactcca tcaccatgga atttaagaaa gattccgtca gacactcctg ctcggtgccg 1380 tatgaagtga aatttaatcc tgtaggcaga gaactctata ctcatccccc agaacacgga 1440 gtagagcaag cgtgccaagt ctacgcacat gatgcacaga acagaggagc ttatgtcgag 1500 atgcacctcc cgggctcaga agtggacagc agtttggttt ccttgagcgg cagttcagtc 1560 accgtgacac ctcctgatgg gactagcgcc ctggtggaat gcgagtgtgg ctccggagga 1620 tccggcacaa agatctccga gaccatcaac aagacaaaac agttcagcca gtgcacaaag 1680 aaggagcagt gcagagcata tcggctgcag aacgataagt gggtgtataa ttctgacaaa 1740 ctgcccaaag cagcgggagc caccttaaaa ggaaaactgc atgtcccatt cttgctggca 1800 gacggcaaat gcaccgtgcc tctagcacca gaacctatga taaccttcgg tttcagatca 1860 gtgtcactga aactgcaccc taagaatccc acatatctaa tcacccgcca acttgctgat 1920 gagcctcact acacgcacga gctcatatct gaaccagctg ttaggaattt taccgtcacc 1980 gaaaaagggt gggagtttgt atggggaaac cacccgccga aaaggttttg ggcacaggaa 2040 acagcacccg gaaatccaca tgggctaccg cacgaggtga taactcatta ttaccacaga 2100 taccctatgt ccaccatcct gggtttgtca atttgtgccg ccattgcaac cgtttccgtt 2160 gcagcgtcta cctggctgtt ttgcagatca agagttgcgt gcctaactcc ttaccggcta 2220 acacctaacg ctaggatacc attttgtctg gctgtgcttt gctgcgcccg cactgcccgg 2280 gccgagacca cctgggagtc cttggatcac ctatggaaca ataaccaaca gatgttctgg 2340 attcaattgc tgatccctct ggccgccttg atcgtagtga ctcgcctgct caggtgcgtg 2400 tgctgtgtcg tgcctttttt agtcatggcc ggcgccgcag gcgccggcgc ctacgagcac 2460 gcgaccacga tgccgagcca agcgggaatc tcgtataaca ctatagtcaa cagagcaggc 2520 tacgcaccac tccctatcag cataacacca acaaagatca agctgatacc tacagtgaac 2580 ttggagtacg tcacctgcca ctacaaaaca ggaatggatt caccagccat caaatgctgc 2640 ggatctcagg aatgcactcc aacttacagg cctgatgaac agtgcaaagt cttcacaggg 2700 gtttacccgt tcatgtgggg tggtgcatat tgcttttgcg acactgagaa cacccaagtc 2760 agcaaggcct acgtaatgaa atctgacgac tgccttgcgg atcatgctga agcatataaa 2820 gcgcacacag cctcagtgca ggcgttcctc aacatcacag tgggagaaca ctctattgtg 2880 actaccgtgt atgtgaatgg agaaactcct gtgaatttca atggggtcaa aataactgca 2940 ggtccgcttt ccacagcttg gacacccttt gatcgcaaaa tcgtgcagta tgccggggag 3000 atctataatt atgattttcc tgagtatggg gcaggacaac caggagcatt tggagatata 3060 caatccagaa cagtctcaag ctctgatctg tatgccaata ccaacctagt gctgcagaga 3120 cccaaagcag gagcgatcca cgtgccatac actcaggcac cttcgggttt tgagcaatgg 3180 aagaaagata aagctccatc attgaaattt accgcccctt tcggatgcga aatatataca 3240 aaccccattc gcgccgaaaa ctgtgctgta gggtcaattc cattagcctt tgacattccc 3300 gacgccttgt tcaccagggt gtcagaaaca ccgacacttt cagcggccga atgcactctt 3360 aacgagtgcg tgtattcttc cgactttggt gggatcgcca cggtcaagta ctcggccagc 3420 aagtcaggca agtgcgcagt ccatgtgcca tcagggactg ctaccctaaa agaagcagca 3480 gtcgagctaa ccgagcaagg gtcggcgact atccatttct cgaccgcaaa tatccacccg 3540 gagttcaggc tccaaatatg cacatcatat gttacgtgca aaggtgattg tcaccccccg 3600 aaagaccata ttgtgacaca ccctcagtat cacgcccaaa catttacagc cgcggtgtca 3660 aaaaccgcgt ggacgtggtt aacatccctg ctgggaggat cagccgtaat tattataatt 3720 ggcttggtgc tggctactat tgtggccatg tacgtgctga ccaaccagaa acataat 3777 <210> 22 <211> 1259 <212> PRT <213> Artificial <220> <223> VLP_VEEV VLP 538 vector-VEEV VLP <400> 22 Met Phe Pro Phe Gln Pro Met Tyr Pro Met Gln Pro Met Pro Tyr Arg 1 5 10 15 Asn Pro Phe Ala Ala Pro Arg Arg Pro Trp Phe Pro Arg Thr Asp Pro 20 25 30 Phe Leu Ala Met Gln Val Gln Glu Leu Thr Arg Ser Met Ala Asn Leu 35 40 45 Thr Phe Lys Gln Arg Arg Asp Ala Pro Pro Glu Gly Pro Ser Ala Asn 50 55 60 Lys Pro Lys Lys Glu Ala Ser Gln Lys Gln Lys Gly Gly Gly Gln Gly 65 70 75 80 Lys Lys Lys Lys Asn Gln Gly Lys Lys Lys Ala Lys Thr Gly Pro Pro 85 90 95 Asn Pro Lys Ala Gln Asn Gly Asn Lys Lys Lys Thr Asn Lys Lys Pro 100 105 110 Gly Lys Arg Gln Arg Met Val Met Lys Leu Glu Ser Asp Lys Thr Phe 115 120 125 Pro Ile Met Leu Glu Gly Lys Ile Asn Gly Tyr Ala Cys Val Val Gly 130 135 140 Gly Lys Leu Phe Arg Pro Met His Val Glu Gly Lys Ile Asp Asn Asp 145 150 155 160 Val Leu Ala Ala Leu Lys Thr Lys Lys Ala Ser Lys Tyr Asp Leu Glu 165 170 175 Tyr Ala Asp Val Pro Gln Asn Met Arg Ala Asp Thr Phe Lys Tyr Thr 180 185 190 His Glu Lys Pro Gln Gly Tyr Tyr Ser Trp His His Gly Ala Val Gln 195 200 205 Tyr Glu Asn Gly Arg Phe Thr Val Pro Lys Gly Val Gly Ala Lys Gly 210 215 220 Asp Ser Gly Arg Pro Ile Leu Asp Asn Gln Gly Arg Val Val Ala Ile 225 230 235 240 Val Leu Gly Gly Val Asn Glu Gly Ser Arg Thr Ala Leu Ser Val Val 245 250 255 Met Trp Asn Glu Lys Gly Val Thr Val Lys Tyr Thr Pro Glu Asn Cys 260 265 270 Glu Gln Trp Ser Leu Val Thr Thr Met Cys Leu Leu Ala Asn Val Thr 275 280 285 Phe Pro Cys Ala Gln Pro Pro Ile Cys Tyr Asp Arg Lys Pro Ala Glu 290 295 300 Thr Leu Ala Met Leu Ser Val Asn Val Asp Asn Pro Gly Tyr Asp Glu 305 310 315 320 Leu Leu Glu Ala Ala Val Lys Cys Pro Gly Arg Lys Arg Arg Ser Thr 325 330 335 Glu Glu Leu Phe Asn Glu Tyr Lys Leu Thr Arg Pro Tyr Met Ala Arg 340 345 350 Cys Ile Arg Cys Ala Val Gly Ser Cys His Ser Pro Ile Ala Ile Glu 355 360 365 Ala Val Lys Ser Asp Gly His Asp Gly Tyr Val Arg Leu Gln Thr Ser 370 375 380 Ser Gln Tyr Gly Leu Asp Ser Ser Gly Asn Leu Lys Gly Arg Thr Met 385 390 395 400 Arg Tyr Asp Met His Gly Thr Ile Lys Glu Ile Pro Leu His Gln Val 405 410 415 Ser Leu Tyr Thr Ser Arg Pro Cys His Ile Val Asp Gly His Gly Tyr 420 425 430 Phe Leu Leu Ala Arg Cys Pro Ala Gly Asp Ser Ile Thr Met Glu Phe 435 440 445 Lys Lys Asp Ser Val Arg His Ser Cys Ser Val Pro Tyr Glu Val Lys 450 455 460 Phe Asn Pro Val Gly Arg Glu Leu Tyr Thr His Pro Pro Glu His Gly 465 470 475 480 Val Glu Gln Ala Cys Gln Val Tyr Ala His Asp Ala Gln Asn Arg Gly 485 490 495 Ala Tyr Val Glu Met His Leu Pro Gly Ser Glu Val Asp Ser Ser Leu 500 505 510 Val Ser Leu Ser Gly Ser Ser Val Thr Val Thr Pro Pro Asp Gly Thr 515 520 525 Ser Ala Leu Val Glu Cys Glu Cys Gly Ser Gly Gly Ser Gly Thr Lys 530 535 540 Ile Ser Glu Thr Ile Asn Lys Thr Lys Gln Phe Ser Gln Cys Thr Lys 545 550 555 560 Lys Glu Gln Cys Arg Ala Tyr Arg Leu Gln Asn Asp Lys Trp Val Tyr 565 570 575 Asn Ser Asp Lys Leu Pro Lys Ala Ala Gly Ala Thr Leu Lys Gly Lys 580 585 590 Leu His Val Pro Phe Leu Leu Ala Asp Gly Lys Cys Thr Val Pro Leu 595 600 605 Ala Pro Glu Pro Met Ile Thr Phe Gly Phe Arg Ser Val Ser Leu Lys 610 615 620 Leu His Pro Lys Asn Pro Thr Tyr Leu Ile Thr Arg Gln Leu Ala Asp 625 630 635 640 Glu Pro His Tyr Thr His Glu Leu Ile Ser Glu Pro Ala Val Arg Asn 645 650 655 Phe Thr Val Thr Glu Lys Gly Trp Glu Phe Val Trp Gly Asn His Pro 660 665 670 Pro Lys Arg Phe Trp Ala Gln Glu Thr Ala Pro Gly Asn Pro His Gly 675 680 685 Leu Pro His Glu Val Ile Thr His Tyr Tyr His Arg Tyr Pro Met Ser 690 695 700 Thr Ile Leu Gly Leu Ser Ile Cys Ala Ala Ile Ala Thr Val Ser Val 705 710 715 720 Ala Ala Ser Thr Trp Leu Phe Cys Arg Ser Arg Val Ala Cys Leu Thr 725 730 735 Pro Tyr Arg Leu Thr Pro Asn Ala Arg Ile Pro Phe Cys Leu Ala Val 740 745 750 Leu Cys Cys Ala Arg Thr Ala Arg Ala Glu Thr Thr Trp Glu Ser Leu 755 760 765 Asp His Leu Trp Asn Asn Asn Gln Gln Met Phe Trp Ile Gln Leu Leu 770 775 780 Ile Pro Leu Ala Ala Leu Ile Val Val Thr Arg Leu Leu Arg Cys Val 785 790 795 800 Cys Cys Val Val Pro Phe Leu Val Met Ala Gly Ala Ala Gly Ala Gly 805 810 815 Ala Tyr Glu His Ala Thr Thr Met Pro Ser Gln Ala Gly Ile Ser Tyr 820 825 830 Asn Thr Ile Val Asn Arg Ala Gly Tyr Ala Pro Leu Pro Ile Ser Ile 835 840 845 Thr Pro Thr Lys Ile Lys Leu Ile Pro Thr Val Asn Leu Glu Tyr Val 850 855 860 Thr Cys His Tyr Lys Thr Gly Met Asp Ser Pro Ala Ile Lys Cys Cys 865 870 875 880 Gly Ser Gln Glu Cys Thr Pro Thr Tyr Arg Pro Asp Glu Gln Cys Lys 885 890 895 Val Phe Thr Gly Val Tyr Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe 900 905 910 Cys Asp Thr Glu Asn Thr Gln Val Ser Lys Ala Tyr Val Met Lys Ser 915 920 925 Asp Asp Cys Leu Ala Asp His Ala Glu Ala Tyr Lys Ala His Thr Ala 930 935 940 Ser Val Gln Ala Phe Leu Asn Ile Thr Val Gly Glu His Ser Ile Val 945 950 955 960 Thr Thr Val Tyr Val Asn Gly Glu Thr Pro Val Asn Phe Asn Gly Val 965 970 975 Lys Ile Thr Ala Gly Pro Leu Ser Thr Ala Trp Thr Pro Phe Asp Arg 980 985 990 Lys Ile Val Gln Tyr Ala Gly Glu Ile Tyr Asn Tyr Asp Phe Pro Glu 995 1000 1005 Tyr Gly Ala Gly Gln Pro Gly Ala Phe Gly Asp Ile Gln Ser Arg 1010 1015 1020 Thr Val Ser Ser Ser Asp Leu Tyr Ala Asn Thr Asn Leu Val Leu 1025 1030 1035 Gln Arg Pro Lys Ala Gly Ala Ile His Val Pro Tyr Thr Gln Ala 1040 1045 1050 Pro Ser Gly Phe Glu Gln Trp Lys Lys Asp Lys Ala Pro Ser Leu 1055 1060 1065 Lys Phe Thr Ala Pro Phe Gly Cys Glu Ile Tyr Thr Asn Pro Ile 1070 1075 1080 Arg Ala Glu Asn Cys Ala Val Gly Ser Ile Pro Leu Ala Phe Asp 1085 1090 1095 Ile Pro Asp Ala Leu Phe Thr Arg Val Ser Glu Thr Pro Thr Leu 1100 1105 1110 Ser Ala Ala Glu Cys Thr Leu Asn Glu Cys Val Tyr Ser Ser Asp 1115 1120 1125 Phe Gly Gly Ile Ala Thr Val Lys Tyr Ser Ala Ser Lys Ser Gly 1130 1135 1140 Lys Cys Ala Val His Val Pro Ser Gly Thr Ala Thr Leu Lys Glu 1145 1150 1155 Ala Ala Val Glu Leu Thr Glu Gln Gly Ser Ala Thr Ile His Phe 1160 1165 1170 Ser Thr Ala Asn Ile His Pro Glu Phe Arg Leu Gln Ile Cys Thr 1175 1180 1185 Ser Tyr Val Thr Cys Lys Gly Asp Cys His Pro Pro Lys Asp His 1190 1195 1200 Ile Val Thr His Pro Gln Tyr His Ala Gln Thr Phe Thr Ala Ala 1205 1210 1215 Val Ser Lys Thr Ala Trp Thr Trp Leu Thr Ser Leu Leu Gly Gly 1220 1225 1230 Ser Ala Val Ile Ile Ile Ile Gly Leu Val Leu Ala Thr Ile Val 1235 1240 1245 Ala Met Tyr Val Leu Thr Asn Gln Lys His Asn 1250 1255 <210> 23 <211> 8416 <212> DNA <213> Artificial <220> <223> VLP_CHI 520 vector <400> 23 gaattcccat tgcatacgtt gtatccatat cataatatgt acatttatat tggctcatgt 60 ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta atcaattacg 120 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 180 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 240 atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 300 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 360 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 420 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 480 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 540 gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 600 tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 660 gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt tgacctccat 720 agaagacacc gggaccgatc cagcctccgt taacggtgga gggcagtgta gtctgagcag 780 tactcgttgc tgccgcgcgc gccaccagac ataatagctg acagactaac agactgttcc 840 tttccatggg tcttttctgc agtcaccgtc gtcgacacgt gtgatcagat atcgcggccg 900 ccaccatgga gttcatcccg acgcaaactt tctataacag aaggtaccaa ccccgaccct 960 gggccccacg ccctacaatt caagtaatta gacctagacc acgtccacag aggcaggctg 1020 ggcaactcgc ccagctgatc tccgcagtca acaaattgac catgcgcgcg gtacctcaac 1080 agaagcctcg cagaaatcgg aaaaacaaga agcaaaggca gaagaagcag gcgccgcaaa 1140 acgacccaaa gcaaaagaag caaccaccac aaaagaagcc ggctcaaaag aagaagaaac 1200 caggccgtag ggagagaatg tgcatgaaaa ttgaaaatga ttgcatcttc gaagtcaagc 1260 atgaaggcaa agtgatgggc tacgcatgcc tggtggggga taaagtaatg aaaccagcac 1320 atgtgaaggg aactatcgac aatgccgatc tggctaaact ggcctttaag cggtcgtcta 1380 aatacgatct tgaatgtgca cagataccgg tgcacatgaa gtctgatgcc tcgaagttta 1440 cccacgagaa acccgagggg tactataact ggcatcacgg agcagtgcag tattcaggag 1500 gccggttcac tatcccgacg ggtgcaggca agccgggaga cagcggcaga ccgatcttcg 1560 acaacaaagg acgggtggtg gccatcgtcc taggaggggc caacgaaggt gcccgcacgg 1620 ccctctccgt ggtgacgtgg aacaaagaca tcgtcacaaa aattacccct gagggagccg 1680 aagagtggag cctcgccctc ccggtcttgt gcctgttggc aaacactaca ttcccctgct 1740 ctcagccgcc ttgcacaccc tgctgctacg aaaaggaacc ggaaagcacc ttgcgcatgc 1800 ttgaggacaa cgtgatgaga cccggatact accagctact aaaagcatcg ctgacttgct 1860 ctccccaccg ccaaagacgc agtactaagg acaattttaa tgtctataaa gccacaagac 1920 catatctagc tcattgtcct gactgcggag aagggcattc gtgccacagc cctatcgcat 1980 tggagcgcat cagaaatgaa gcaacggacg gaacgctgaa aatccaggtc tctttgcaga 2040 tcgggataaa gacagatgac agccacgatt ggaccaagct gcgctatatg gatagccata 2100 cgccagcgga cgcggagcga gccggattgc ttgtaaggac ttcagcaccg tgcacgatca 2160 ccgggaccat gggacacttt attctcgccc gatgcccgaa aggagagacg ctgacagtgg 2220 gatttacgga cagcagaaag atcagccaca catgcacaca cccgttccat catgaaccac 2280 ctgtgatagg tagggagagg ttccactctc gaccacaaca tggtaaagag ttaccttgca 2340 gcacgtacgt gcagagcacc gctgccactg ctgaggagat agaggtgcat atgcccccag 2400 atactcctga ccgcacgctg atgacgcagc agtctggcaa cgtgaagatc acagttaatg 2460 gctccggagg atccggcggg cagacggtgc ggtacaagtg caactgcggt ggctcaaacg 2520 agggactgac aaccacagac aaagtgatca ataactgcaa aattgatcag tgccatgctg 2580 cagtcactaa tcacaagaat tggcaataca actccccttt agtcccgcgc aacgctgaac 2640 tcggggaccg taaaggaaag atccacatcc cattcccatt ggcaaacgtg acttgcagag 2700 tgccaaaagc aagaaaccct acagtaactt acggaaaaaa ccaagtcacc atgctgctgt 2760 atcctgacca tccgacactc ttgtcttacc gtaacatggg acaggaacca aattaccacg 2820 aggagtgggt gacacacaag aaggaggtta ccttgaccgt gcctactgag ggtctggagg 2880 tcacttgggg caacaacgaa ccatacaagt actggccgca gatgtctacg aacggtactg 2940 ctcatggtca cccacatgag ataatcttgt actattatga gctgtacccc actatgactg 3000 tagtcattgt gtcggtggcc tcgttcgtgc ttctgtcgat ggtgggcaca gcagtgggaa 3060 tgtgtgtgtg cgcacggcgc agatgcatta caccatatga attaacacca ggagccactg 3120 ttcccttcct gctcagcctg ctatgctgcg tcagaacgac caaggcggcc acatattacg 3180 aggctgcggc atatctatgg aacgaacagc agcccctgtt ctggttgcag gctcttatcc 3240 cgctggccgc cttgatcgtc ctgtgcaact gtctgaaact cttgccatgc tgctgtaaga 3300 ccctggcttt tttagccgta atgagcatcg gtgcccacac tgtgagcgcg tacgaacacg 3360 taacagtgat cccgaacacg gtgggagtac cgtataagac tcttgtcaac agaccgggtt 3420 acagccccat ggtgttggag atggagctac aatcagtcac cttggaacca acactgtcac 3480 ttgactacat cacgtgcgag tacaaaactg tcatcccctc cccgtacgtg aagtgctgtg 3540 gtacagcaga gtgcaaggac aagagcctac cagactacag ctgcaaggtc tttactggag 3600 tctacccatt tatgtggggc ggcgcctact gcttttgcga cgccgaaaat acgcaattga 3660 gcgaggcaca tgtagagaaa tctgaatctt gcaaaacaga gtttgcatcg gcctacagag 3720 cccacaccgc atcggcgtcg gcgaagctcc gcgtccttta ccaaggaaac aacattaccg 3780 tagctgccta cgctaacggt gaccatgccg tcacagtaaa ggacgccaag tttgtcgtgg 3840 gcccaatgtc ctccgcctgg acaccttttg acaacaaaat cgtggtgtac aaaggcgacg 3900 tctacaacat ggactaccca ccttttggcg caggaagacc aggacaattt ggtgacattc 3960 aaagtcgtac accggaaagt aaagacgttt atgccaacac tcagttggta ctacagaggc 4020 cagcagcagg cacggtacat gtaccatact ctcaggcacc atctggcttc aagtattggc 4080 tgaaggaacg aggagcatcg ctacagcaca cggcaccgtt cggttgccag attgcgacaa 4140 acccggtaag agctgtaaat tgcgctgtgg ggaacatacc aatttccatc gacataccgg 4200 atgcggcctt tactagggtt gtcgatgcac cctctgtaac ggacatgtca tgcgaagtac 4260 cagcctgcac tcactcctcc gactttgggg gcgtcgccat catcaaatac acagctagca 4320 agaaaggtaa atgtgcagta cattcgatga ccaacgccgt taccattcga gaagccgacg 4380 tagaagtaga ggggaactcc cagctgcaaa tatccttctc aacagccctg gcaagcgccg 4440 agtttcgcgt gcaagtgtgc tccacacaag tacactgcgc agccgcatgc caccctccaa 4500 aggaccacat agtcaattac ccagcatcac acaccaccct tggggtccag gatatatcca 4560 caacggcaat gtcttgggtg cagaagatta cgggaggagt aggattaatt gttgctgttg 4620 ctgccttaat tttaattgtg gtgctatgcg tgtcgtttag caggcactaa ggatctagat 4680 ctgctgtgcc ttctagttgc cagccatctg ttgtttgccc ctcccccgtg ccttccttga 4740 ccctggaagg tgccactccc actgtccttt cctaataaaa tgaggaaatt gcatcgcatt 4800 gtctgagtag gtgtcattct attctggggg gtggggtggg gcaggacagc aagggggagg 4860 attgggaaga caatagcagg catgctgggg atgcggtggg ctctatgggt acccaggtgc 4920 tgaagaattg acccggttcc tcctgggcca gaaagaagca ggcacatccc cttctctgtg 4980 acacaccctg tccacgcccc tggttcttag ttccagcccc actcatagga cactcatagc 5040 tcaggagggc tccgccttca atcccacccg ctaaagtact tggagcggtc tctccctccc 5100 tcatcagccc accaaaccaa acctagcctc caagagtggg aagaaattaa agcaagatag 5160 gctattaagt gcagagggag agaaaatgcc tccaacatgt gaggaagtaa tgagagaaat 5220 catagaattt taaggccatg atttaaggcc atcatggcct aagcttgaaa ggagatagga 5280 tcaaagcttg gcgtaatcat ggtcatagct gtttcctgtg tgaaattgtt atccgctcac 5340 aattccacac aacatacgag ccggaagcat aaagtgtaaa gcctggggtg cctaatgagt 5400 gagctaactc acattaattg cgttgcgctc actgcccgct ttccagtcgg gaaacctgtc 5460 gtgccagctg cattaatgaa tcggccaacg cgcggggaga ggcggtttgc gtattgggcg 5520 ctcttccgct tcctcgctca ctgactcgct gcgctcggtc gttcggctgc ggcgagcggt 5580 atcagctcac tcaaaggcgg taatacggtt atccacagaa tcaggggata acgcaggaaa 5640 gaacatgtga gcaaaaggcc agcaaaaggc caggaaccgt aaaaaggccg cgttgctggc 5700 gtttttccat aggctccgcc cccctgacga gcatcacaaa aatcgacgct caagtcagag 5760 gtggcgaaac ccgacaggac tataaagata ccaggcgttt ccccctggaa gctccctcgt 5820 gcgctctcct gttccgaccc tgccgcttac cggatacctg tccgcctttc tcccttcggg 5880 aagcgtggcg ctttctcata gctcacgctg taggtatctc agttcggtgt aggtcgttcg 5940 ctccaagctg ggctgtgtgc acgaaccccc cgttcagccc gaccgctgcg ccttatccgg 6000 taactatcgt cttgagtcca acccggtaag acacgactta tcgccactgg cagcagccac 6060 tggtaacagg attagcagag cgaggtatgt aggcggtgct acagagttct tgaagtggtg 6120 gcctaactac ggctacacta gaagaacagt atttggtatc tgcgctctgc tgaagccagt 6180 taccttcgga aaaagagttg gtagctcttg atccggcaaa caaaccaccg ctggtagcgg 6240 tggttttttt gtttgcaagc agcagattac gcgcagaaaa aaaggatctc aagaagatcc 6300 tttgatcttt tctacggggt ctgacgctca gtggaacgaa aactcacgtt aagggatttt 6360 ggtcatgaga ttatcaaaaa ggatcttcac ctagatcctt ttaaattaaa aatgaagttt 6420 taaatcaatc taaagtatat atgagtaaac ttggtctgac agttaccaat gcttaatcag 6480 tgaggcacct atctcagcga tctgtctatt tcgttcatcc atagttgcct gactccccgt 6540 cgtgtagata actacgatac gggagggctt accatctggc cccagtgctg caatgatacc 6600 gcgagaacca cgctcaccgg ctccagattt atcagcaata aaccagccag ccggaagggc 6660 cgagcgcaga agtggtcctg caactttatc cgcctccatc cagtctatta attgttgccg 6720 ggaagctaga gtaagtagtt cgccagttaa tagtttgcgc aacgttgttg ccattgctac 6780 aggcatcgtg gtgtcacgct cgtcgtttgg tatggcttca ttcagctccg gttcccaacg 6840 atcaaggcga gttacatgat cccccatgtt gtgcaaaaaa gcggttagct ccttcggtcc 6900 tccgatcgtt gtcagaagta agttggccgc agtgttatca ctcatggtta tggcagcact 6960 gcataattct cttactgtca tgccatccgt aagatgcttt tctgtgactg gtgagtactc 7020 aaccaagtca ttctgagaat agtgtatgcg gcgaccgagt tgctcttgcc cggcgtcaat 7080 acgggataat accgcgccac atagcagaac tttaaaagtg ctcatcattg gaaaacgttc 7140 ttcggggcga aaactctcaa ggatcttacc gctgttgaga tccagttcga tgtaacccac 7200 tcgtgcaccc aactgatctt cagcatcttt tactttcacc agcgtttctg ggtgagcaaa 7260 aacaggaagg caaaatgccg caaaaaaggg aataagggcg acacggaaat gttgaatact 7320 catactcttc ctttttcaat attattgaag catttatcag ggttattgtc tcatgagcgg 7380 atacatattt gaatgtattt agaaaaataa acaaataggg gttccgcgca catttccccg 7440 aaaagtgcca cctgacgtct aagaaaccat tattatcatg acattaacct ataaaaatag 7500 gcgtatcacg aggccctttc gggtcgcgcg tttcggtgat gacggtgaaa acctctgaca 7560 catgcagctc ccgttgacgg tcacagcttg tctgtaagcg gatgccggga gcagacaagc 7620 ccgtcagggc gcgtcagcgg gtgttggcgg gtgtcggggc tggcttaact atgcggcatc 7680 agagcagatt gtactgagag tgcaccataa aattgtaaac gttaatattt tgttaaaatt 7740 cgcgttaaat ttttgttaaa tcagctcatt ttttaaccaa taggccgaaa tcggcaaaat 7800 cccttataaa tcaaaagaat agcccgagat agggttgagt gttgttccag tttggaacaa 7860 gagtccacta ttaaagaacg tggactccaa cgtcaaaggg cgaaaaaccg tctatcaggg 7920 cgatggccca ctacgtgaac catcacccaa atcaagtttt ttggggtcga ggtgccgtaa 7980 agcactaaat cggaacccta aagggagccc ccgatttaga gcttgacggg gaaagccggc 8040 gaacgtggcg agaaaggaag ggaagaaagc gaaaggagcg ggcgctaggg cgctggcaag 8100 tgtagcggtc acgctgcgcg taaccaccac acccgccgcg cttaatgcgc cgctacaggg 8160 cgcgtactat ggttgctttg acgtatgcgg tgtgaaatac cgcacagatg cgtaaggaga 8220 aaataccgca tcaggcgcca ttcgccattc aggctgcgca actgttggga agggcgatcg 8280 gtgcgggcct cttcgctatt acgccagctg gcgaaagggg gatgtgctgc aaggcgatta 8340 agttgggtaa cgccagggtt ttcccagtca cgacgttgta aaacgacggc cagtgaattc 8400 catggtctca actttc 8416 <210> 24 <211> 3762 <212> DNA <213> Artificial <220> <223> VLP_CHI 520 vector insert <400> 24 atggagttca tcccgacgca aactttctat aacagaaggt accaaccccg accctgggcc 60 ccacgcccta caattcaagt aattagacct agaccacgtc cacagaggca ggctgggcaa 120 ctcgcccagc tgatctccgc agtcaacaaa ttgaccatgc gcgcggtacc tcaacagaag 180 cctcgcagaa atcggaaaaa caagaagcaa aggcagaaga agcaggcgcc gcaaaacgac 240 ccaaagcaaa agaagcaacc accacaaaag aagccggctc aaaagaagaa gaaaccaggc 300 cgtagggaga gaatgtgcat gaaaattgaa aatgattgca tcttcgaagt caagcatgaa 360 ggcaaagtga tgggctacgc atgcctggtg ggggataaag taatgaaacc agcacatgtg 420 aagggaacta tcgacaatgc cgatctggct aaactggcct ttaagcggtc gtctaaatac 480 gatcttgaat gtgcacagat accggtgcac atgaagtctg atgcctcgaa gtttacccac 540 gagaaacccg aggggtacta taactggcat cacggagcag tgcagtattc aggaggccgg 600 ttcactatcc cgacgggtgc aggcaagccg ggagacagcg gcagaccgat cttcgacaac 660 aaaggacggg tggtggccat cgtcctagga ggggccaacg aaggtgcccg cacggccctc 720 tccgtggtga cgtggaacaa agacatcgtc acaaaaatta cccctgaggg agccgaagag 780 tggagcctcg ccctcccggt cttgtgcctg ttggcaaaca ctacattccc ctgctctcag 840 ccgccttgca caccctgctg ctacgaaaag gaaccggaaa gcaccttgcg catgcttgag 900 gacaacgtga tgagacccgg atactaccag ctactaaaag catcgctgac ttgctctccc 960 caccgccaaa gacgcagtac taaggacaat tttaatgtct ataaagccac aagaccatat 1020 ctagctcatt gtcctgactg cggagaaggg cattcgtgcc acagccctat cgcattggag 1080 cgcatcagaa atgaagcaac ggacggaacg ctgaaaatcc aggtctcttt gcagatcggg 1140 ataaagacag atgacagcca cgattggacc aagctgcgct atatggatag ccatacgcca 1200 gcggacgcgg agcgagccgg attgcttgta aggacttcag caccgtgcac gatcaccggg 1260 accatgggac actttattct cgcccgatgc ccgaaaggag agacgctgac agtgggattt 1320 acggacagca gaaagatcag ccacacatgc acacacccgt tccatcatga accacctgtg 1380 ataggtaggg agaggttcca ctctcgacca caacatggta aagagttacc ttgcagcacg 1440 tacgtgcaga gcaccgctgc cactgctgag gagatagagg tgcatatgcc cccagatact 1500 cctgaccgca cgctgatgac gcagcagtct ggcaacgtga agatcacagt taatggctcc 1560 ggaggatccg gcgggcagac ggtgcggtac aagtgcaact gcggtggctc aaacgaggga 1620 ctgacaacca cagacaaagt gatcaataac tgcaaaattg atcagtgcca tgctgcagtc 1680 actaatcaca agaattggca atacaactcc cctttagtcc cgcgcaacgc tgaactcggg 1740 gaccgtaaag gaaagatcca catcccattc ccattggcaa acgtgacttg cagagtgcca 1800 aaagcaagaa accctacagt aacttacgga aaaaaccaag tcaccatgct gctgtatcct 1860 gaccatccga cactcttgtc ttaccgtaac atgggacagg aaccaaatta ccacgaggag 1920 tgggtgacac acaagaagga ggttaccttg accgtgccta ctgagggtct ggaggtcact 1980 tggggcaaca acgaaccata caagtactgg ccgcagatgt ctacgaacgg tactgctcat 2040 ggtcacccac atgagataat cttgtactat tatgagctgt accccactat gactgtagtc 2100 attgtgtcgg tggcctcgtt cgtgcttctg tcgatggtgg gcacagcagt gggaatgtgt 2160 gtgtgcgcac ggcgcagatg cattacacca tatgaattaa caccaggagc cactgttccc 2220 ttcctgctca gcctgctatg ctgcgtcaga acgaccaagg cggccacata ttacgaggct 2280 gcggcatatc tatggaacga acagcagccc ctgttctggt tgcaggctct tatcccgctg 2340 gccgccttga tcgtcctgtg caactgtctg aaactcttgc catgctgctg taagaccctg 2400 gcttttttag ccgtaatgag catcggtgcc cacactgtga gcgcgtacga acacgtaaca 2460 gtgatcccga acacggtggg agtaccgtat aagactcttg tcaacagacc gggttacagc 2520 cccatggtgt tggagatgga gctacaatca gtcaccttgg aaccaacact gtcacttgac 2580 tacatcacgt gcgagtacaa aactgtcatc ccctccccgt acgtgaagtg ctgtggtaca 2640 gcagagtgca aggacaagag cctaccagac tacagctgca aggtctttac tggagtctac 2700 ccatttatgt ggggcggcgc ctactgcttt tgcgacgccg aaaatacgca attgagcgag 2760 gcacatgtag agaaatctga atcttgcaaa acagagtttg catcggccta cagagcccac 2820 accgcatcgg cgtcggcgaa gctccgcgtc ctttaccaag gaaacaacat taccgtagct 2880 gcctacgcta acggtgacca tgccgtcaca gtaaaggacg ccaagtttgt cgtgggccca 2940 atgtcctccg cctggacacc ttttgacaac aaaatcgtgg tgtacaaagg cgacgtctac 3000 aacatggact acccaccttt tggcgcagga agaccaggac aatttggtga cattcaaagt 3060 cgtacaccgg aaagtaaaga cgtttatgcc aacactcagt tggtactaca gaggccagca 3120 gcaggcacgg tacatgtacc atactctcag gcaccatctg gcttcaagta ttggctgaag 3180 gaacgaggag catcgctaca gcacacggca ccgttcggtt gccagattgc gacaaacccg 3240 gtaagagctg taaattgcgc tgtggggaac ataccaattt ccatcgacat accggatgcg 3300 gcctttacta gggttgtcga tgcaccctct gtaacggaca tgtcatgcga agtaccagcc 3360 tgcactcact cctccgactt tgggggcgtc gccatcatca aatacacagc tagcaagaaa 3420 ggtaaatgtg cagtacattc gatgaccaac gccgttacca ttcgagaagc cgacgtagaa 3480 gtagagggga actcccagct gcaaatatcc ttctcaacag ccctggcaag cgccgagttt 3540 cgcgtgcaag tgtgctccac acaagtacac tgcgcagccg catgccaccc tccaaaggac 3600 cacatagtca attacccagc atcacacacc acccttgggg tccaggatat atccacaacg 3660 gcaatgtctt gggtgcagaa gattacggga ggagtaggat taattgttgc tgttgctgcc 3720 ttaattttaa ttgtggtgct atgcgtgtcg tttagcaggc ac 3762 <210> 25 <211> 1254 <212> PRT <213> Artificial <220> <223> VLP_CHI 520 vector <400> 25 Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro 1 5 10 15 Arg Pro Trp Ala Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30 Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45 Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60 Arg Lys Asn Lys Lys Gln Arg Gln Lys Lys Gln Ala Pro Gln Asn Asp 65 70 75 80 Pro Lys Gln Lys Lys Gln Pro Pro Gln Lys Lys Pro Ala Gln Lys Lys 85 90 95 Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110 Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Met Gly Tyr Ala Cys 115 120 125 Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140 Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr 145 150 155 160 Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175 Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190 Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205 Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220 Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu 225 230 235 240 Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255 Gly Ala Glu Glu Trp Ser Leu Ala Leu Pro Val Leu Cys Leu Leu Ala 260 265 270 Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285 Glu Lys Glu Pro Glu Ser Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300 Arg Pro Gly Tyr Tyr Gln Leu Leu Lys Ala Ser Leu Thr Cys Ser Pro 305 310 315 320 His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335 Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350 Cys His Ser Pro Ile Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365 Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380 Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Ser His Thr Pro 385 390 395 400 Ala Asp Ala Glu Arg Ala Gly Leu Leu Val Arg Thr Ser Ala Pro Cys 405 410 415 Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430 Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445 Thr Cys Thr His Pro Phe His His Glu Pro Pro Val Ile Gly Arg Glu 450 455 460 Arg Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr 465 470 475 480 Tyr Val Gln Ser Thr Ala Ala Thr Ala Glu Glu Ile Glu Val His Met 485 490 495 Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Thr Gln Gln Ser Gly Asn 500 505 510 Val Lys Ile Thr Val Asn Gly Ser Gly Gly Ser Gly Gly Gln Thr Val 515 520 525 Arg Tyr Lys Cys Asn Cys Gly Gly Ser Asn Glu Gly Leu Thr Thr Thr 530 535 540 Asp Lys Val Ile Asn Asn Cys Lys Ile Asp Gln Cys His Ala Ala Val 545 550 555 560 Thr Asn His Lys Asn Trp Gln Tyr Asn Ser Pro Leu Val Pro Arg Asn 565 570 575 Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile Pro Phe Pro Leu 580 585 590 Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn Pro Thr Val Thr 595 600 605 Tyr Gly Lys Asn Gln Val Thr Met Leu Leu Tyr Pro Asp His Pro Thr 610 615 620 Leu Leu Ser Tyr Arg Asn Met Gly Gln Glu Pro Asn Tyr His Glu Glu 625 630 635 640 Trp Val Thr His Lys Lys Glu Val Thr Leu Thr Val Pro Thr Glu Gly 645 650 655 Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys Tyr Trp Pro Gln 660 665 670 Met Ser Thr Asn Gly Thr Ala His Gly His Pro His Glu Ile Ile Leu 675 680 685 Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr Val Val Ile Val Ser Val 690 695 700 Ala Ser Phe Val Leu Leu Ser Met Val Gly Thr Ala Val Gly Met Cys 705 710 715 720 Val Cys Ala Arg Arg Arg Cys Ile Thr Pro Tyr Glu Leu Thr Pro Gly 725 730 735 Ala Thr Val Pro Phe Leu Leu Ser Leu Leu Cys Cys Val Arg Thr Thr 740 745 750 Lys Ala Ala Thr Tyr Tyr Glu Ala Ala Ala Tyr Leu Trp Asn Glu Gln 755 760 765 Gln Pro Leu Phe Trp Leu Gln Ala Leu Ile Pro Leu Ala Ala Leu Ile 770 775 780 Val Leu Cys Asn Cys Leu Lys Leu Leu Pro Cys Cys Cys Lys Thr Leu 785 790 795 800 Ala Phe Leu Ala Val Met Ser Ile Gly Ala His Thr Val Ser Ala Tyr 805 810 815 Glu His Val Thr Val Ile Pro Asn Thr Val Gly Val Pro Tyr Lys Thr 820 825 830 Leu Val Asn Arg Pro Gly Tyr Ser Pro Met Val Leu Glu Met Glu Leu 835 840 845 Gln Ser Val Thr Leu Glu Pro Thr Leu Ser Leu Asp Tyr Ile Thr Cys 850 855 860 Glu Tyr Lys Thr Val Ile Pro Ser Pro Tyr Val Lys Cys Cys Gly Thr 865 870 875 880 Ala Glu Cys Lys Asp Lys Ser Leu Pro Asp Tyr Ser Cys Lys Val Phe 885 890 895 Thr Gly Val Tyr Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp 900 905 910 Ala Glu Asn Thr Gln Leu Ser Glu Ala His Val Glu Lys Ser Glu Ser 915 920 925 Cys Lys Thr Glu Phe Ala Ser Ala Tyr Arg Ala His Thr Ala Ser Ala 930 935 940 Ser Ala Lys Leu Arg Val Leu Tyr Gln Gly Asn Asn Ile Thr Val Ala 945 950 955 960 Ala Tyr Ala Asn Gly Asp His Ala Val Thr Val Lys Asp Ala Lys Phe 965 970 975 Val Val Gly Pro Met Ser Ser Ala Trp Thr Pro Phe Asp Asn Lys Ile 980 985 990 Val Val Tyr Lys Gly Asp Val Tyr Asn Met Asp Tyr Pro Pro Phe Gly 995 1000 1005 Ala Gly Arg Pro Gly Gln Phe Gly Asp Ile Gln Ser Arg Thr Pro 1010 1015 1020 Glu Ser Lys Asp Val Tyr Ala Asn Thr Gln Leu Val Leu Gln Arg 1025 1030 1035 Pro Ala Ala Gly Thr Val His Val Pro Tyr Ser Gln Ala Pro Ser 1040 1045 1050 Gly Phe Lys Tyr Trp Leu Lys Glu Arg Gly Ala Ser Leu Gln His 1055 1060 1065 Thr Ala Pro Phe Gly Cys Gln Ile Ala Thr Asn Pro Val Arg Ala 1070 1075 1080 Val Asn Cys Ala Val Gly Asn Ile Pro Ile Ser Ile Asp Ile Pro 1085 1090 1095 Asp Ala Ala Phe Thr Arg Val Val Asp Ala Pro Ser Val Thr Asp 1100 1105 1110 Met Ser Cys Glu Val Pro Ala Cys Thr His Ser Ser Asp Phe Gly 1115 1120 1125 Gly Val Ala Ile Ile Lys Tyr Thr Ala Ser Lys Lys Gly Lys Cys 1130 1135 1140 Ala Val His Ser Met Thr Asn Ala Val Thr Ile Arg Glu Ala Asp 1145 1150 1155 Val Glu Val Glu Gly Asn Ser Gln Leu Gln Ile Ser Phe Ser Thr 1160 1165 1170 Ala Leu Ala Ser Ala Glu Phe Arg Val Gln Val Cys Ser Thr Gln 1175 1180 1185 Val His Cys Ala Ala Ala Cys His Pro Pro Lys Asp His Ile Val 1190 1195 1200 Asn Tyr Pro Ala Ser His Thr Thr Leu Gly Val Gln Asp Ile Ser 1205 1210 1215 Thr Thr Ala Met Ser Trp Val Gln Lys Ile Thr Gly Gly Val Gly 1220 1225 1230 Leu Ile Val Ala Val Ala Ala Leu Ile Leu Ile Val Val Leu Cys 1235 1240 1245 Val Ser Phe Ser Arg His 1250 <210> 26 <211> 8485 <212> DNA <213> Artificial <220> <223> VLP74_11 (CHI VLP 532_NPNAx6) whole sequence <400> 26 gaattcccat tgcatacgtt gtatccatat cataatatgt acatttatat tggctcatgt 60 ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta atcaattacg 120 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 180 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 240 atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 300 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 360 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 420 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 480 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 540 gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 600 tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 660 gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt tgacctccat 720 agaagacacc gggaccgatc cagcctccgt taacggtgga gggcagtgta gtctgagcag 780 tactcgttgc tgccgcgcgc gccaccagac ataatagctg acagactaac agactgttcc 840 tttccatggg tcttttctgc agtcaccgtc gtcgacacgt gtgatcagat atcgcggccg 900 ccaccatgga gttcatcccg acgcaaactt tctataacag aaggtaccaa ccccgaccct 960 gggccccacg ccctacaatt caagtaatta gacctagacc acgtccacag aggcaggctg 1020 ggcaactcgc ccagctgatc tccgcagtca acaaattgac catgcgcgcg gtacctcaac 1080 agaagcctcg cagaaatcgg aaaaacaaga agcaaaggca gaagaagcag gcgccgcaaa 1140 acgacccaaa gcaaaagaag caaccaccac aaaagaagcc ggctcaaaag aagaagaaac 1200 caggccgtag ggagagaatg tgcatgaaaa ttgaaaatga ttgcatcttc gaagtcaagc 1260 atgaaggcaa agtgatgggc tacgcatgcc tggtggggga taaagtaatg aaaccagcac 1320 atgtgaaggg aactatcgac aatgccgatc tggctaaact ggcctttaag cggtcgtcta 1380 aatacgatct tgaatgtgca cagataccgg tgcacatgaa gtctgatgcc tcgaagttta 1440 cccacgagaa acccgagggg tactataact ggcatcacgg agcagtgcag tattcaggag 1500 gccggttcac tatcccgacg ggtgcaggca agccgggaga cagcggcaga ccgatcttcg 1560 acaacaaagg acgggtggtg gccatcgtcc taggaggggc caacgaaggt gcccgcacgg 1620 ccctctccgt ggtgacgtgg aacaaagaca tcgtcacaaa aattacccct gagggagccg 1680 aagagtggag cctcgccctc ccggtcttgt gcctgttggc aaacactaca ttcccctgct 1740 ctcagccgcc ttgcacaccc tgctgctacg aaaaggaacc ggaaagcacc ttgcgcatgc 1800 ttgaggacaa cgtgatgaga cccggatact accagctact aaaagcatcg ctgacttgct 1860 ctccccaccg ccaaagacgc agtactaagg acaattttaa tgtctataaa gccacaagac 1920 catatctagc tcattgtcct gactgcggag aagggcattc gtgccacagc cctatcgcat 1980 tggagcgcat cagaaatgaa gcaacggacg gaacgctgaa aatccaggtc tctttgcaga 2040 tcgggataaa gacagatgac agccacgatt ggaccaagct gcgctatatg gatagccata 2100 cgccagcgga cgcggagcga gccggattgc ttgtaaggac ttcagcaccg tgcacgatca 2160 ccgggaccat gggacacttt attctcgccc gatgcccgaa aggagagacg ctgacagtgg 2220 gatttacgga cagcagaaag atcagccaca catgcacaca cccgttccat catgaaccac 2280 ctgtgatagg tagggagagg ttccactctc gaccacaaca tggtaaagag ttaccttgca 2340 gcacgtacgt gcagagcacc gctgccactg ctgaggagat agaggtgcat atgcccccag 2400 atactcctga ccgcacgctg atgacgcagc agtctggcaa cgtgaagatc acagttaatg 2460 ggcagacggt gcggtacaag tgcaactgcg gtggctccgg aggaaacccg aatgccaatc 2520 ccaacgcgaa ccccaatgct aacccaaatg ccaacccaaa cgccaacccc aacgctggtg 2580 gatccaacga gggactgaca accacagaca aagtgatcaa taactgcaaa attgatcagt 2640 gccatgctgc agtcactaat cacaagaatt ggcaatacaa ctccccttta gtcccgcgca 2700 acgctgaact cggggaccgt aaaggaaaga tccacatccc attcccattg gcaaacgtga 2760 cttgcagagt gccaaaagca agaaacccta cagtaactta cggaaaaaac caagtcacca 2820 tgctgctgta tcctgaccat ccgacactct tgtcttaccg taacatggga caggaaccaa 2880 attaccacga ggagtgggtg acacacaaga aggaggttac cttgaccgtg cctactgagg 2940 gtctggaggt cacttggggc aacaacgaac catacaagta ctggccgcag atgtctacga 3000 acggtactgc tcatggtcac ccacatgaga taatcttgta ctattatgag ctgtacccca 3060 ctatgactgt agtcattgtg tcggtggcct cgttcgtgct tctgtcgatg gtgggcacag 3120 cagtgggaat gtgtgtgtgc gcacggcgca gatgcattac accatatgaa ttaacaccag 3180 gagccactgt tcccttcctg ctcagcctgc tatgctgcgt cagaacgacc aaggcggcca 3240 catattacga ggctgcggca tatctatgga acgaacagca gcccctgttc tggttgcagg 3300 ctcttatccc gctggccgcc ttgatcgtcc tgtgcaactg tctgaaactc ttgccatgct 3360 gctgtaagac cctggctttt ttagccgtaa tgagcatcgg tgcccacact gtgagcgcgt 3420 acgaacacgt aacagtgatc ccgaacacgg tgggagtacc gtataagact cttgtcaaca 3480 gaccgggtta cagccccatg gtgttggaga tggagctaca atcagtcacc ttggaaccaa 3540 cactgtcact tgactacatc acgtgcgagt acaaaactgt catcccctcc ccgtacgtga 3600 agtgctgtgg tacagcagag tgcaaggaca agagcctacc agactacagc tgcaaggtct 3660 ttactggagt ctacccattt atgtggggcg gcgcctactg cttttgcgac gccgaaaata 3720 cgcaattgag cgaggcacat gtagagaaat ctgaatcttg caaaacagag tttgcatcgg 3780 cctacagagc ccacaccgca tcggcgtcgg cgaagctccg cgtcctttac caaggaaaca 3840 acattaccgt agctgcctac gctaacggtg accatgccgt cacagtaaag gacgccaagt 3900 ttgtcgtggg cccaatgtcc tccgcctgga caccttttga caacaaaatc gtggtgtaca 3960 aaggcgacgt ctacaacatg gactacccac cttttggcgc aggaagacca ggacaatttg 4020 gtgacattca aagtcgtaca ccggaaagta aagacgttta tgccaacact cagttggtac 4080 tacagaggcc agcagcaggc acggtacatg taccatactc tcaggcacca tctggcttca 4140 agtattggct gaaggaacga ggagcatcgc tacagcacac ggcaccgttc ggttgccaga 4200 ttgcgacaaa cccggtaaga gctgtaaatt gcgctgtggg gaacatacca atttccatcg 4260 acataccgga tgcggccttt actagggttg tcgatgcacc ctctgtaacg gacatgtcat 4320 gcgaagtacc agcctgcact cactcctccg actttggggg cgtcgccatc atcaaataca 4380 cagctagcaa gaaaggtaaa tgtgcagtac attcgatgac caacgccgtt accattcgag 4440 aagccgacgt agaagtagag gggaactccc agctgcaaat atccttctca acagccctgg 4500 caagcgccga gtttcgcgtg caagtgtgct ccacacaagt acactgcgca gccgcatgcc 4560 accctccaaa ggaccacata gtcaattacc cagcatcaca caccaccctt ggggtccagg 4620 atatatccac aacggcaatg tcttgggtgc agaagattac gggaggagta ggattaattg 4680 ttgctgttgc tgccttaatt ttaattgtgg tgctatgcgt gtcgtttagc aggcactaag 4740 gatctagatc tgctgtgcct tctagttgcc agccatctgt tgtttgcccc tcccccgtgc 4800 cttccttgac cctggaaggt gccactccca ctgtcctttc ctaataaaat gaggaaattg 4860 catcgcattg tctgagtagg tgtcattcta ttctgggggg tggggtgggg caggacagca 4920 agggggagga ttgggaagac aatagcaggc atgctgggga tgcggtgggc tctatgggta 4980 cccaggtgct gaagaattga cccggttcct cctgggccag aaagaagcag gcacatcccc 5040 ttctctgtga cacaccctgt ccacgcccct ggttcttagt tccagcccca ctcataggac 5100 actcatagct caggagggct ccgccttcaa tcccacccgc taaagtactt ggagcggtct 5160 ctccctccct catcagccca ccaaaccaaa cctagcctcc aagagtggga agaaattaaa 5220 gcaagatagg ctattaagtg cagagggaga gaaaatgcct ccaacatgtg aggaagtaat 5280 gagagaaatc atagaatttt aaggccatga tttaaggcca tcatggccta agcttgaaag 5340 gagataggat caaagcttgg cgtaatcatg gtcatagctg tttcctgtgt gaaattgtta 5400 tccgctcaca attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc 5460 ctaatgagtg agctaactca cattaattgc gttgcgctca ctgcccgctt tccagtcggg 5520 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 5580 tattgggcgc tcttccgctt cctcgctcac tgactcgctg cgctcggtcg ttcggctgcg 5640 gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat caggggataa 5700 cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc 5760 gttgctggcg tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc 5820 aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag 5880 ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct 5940 cccttcggga agcgtggcgc tttctcatag ctcacgctgt aggtatctca gttcggtgta 6000 ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc 6060 cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc 6120 agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt 6180 gaagtggtgg cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct 6240 gaagccagtt accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc 6300 tggtagcggt ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca 6360 agaagatcct ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta 6420 agggattttg gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa 6480 atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg 6540 cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg 6600 actccccgtc gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc 6660 aatgataccg cgagaaccac gctcaccggc tccagattta tcagcaataa accagccagc 6720 cggaagggcc gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa 6780 ttgttgccgg gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc 6840 cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg 6900 ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc 6960 cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat 7020 ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg 7080 tgagtactca accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc 7140 ggcgtcaata cgggataata ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg 7200 aaaacgttct tcggggcgaa aactctcaag gatcttaccg ctgttgagat ccagttcgat 7260 gtaacccact cgtgcaccca actgatcttc agcatctttt actttcacca gcgtttctgg 7320 gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga ataagggcga cacggaaatg 7380 ttgaatactc atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct 7440 catgagcgga tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac 7500 atttccccga aaagtgccac ctgacgtcta agaaaccatt attatcatga cattaaccta 7560 taaaaatagg cgtatcacga ggccctttcg ggtcgcgcgt ttcggtgatg acggtgaaaa 7620 cctctgacac atgcagctcc cgttgacggt cacagcttgt ctgtaagcgg atgccgggag 7680 cagacaagcc cgtcagggcg cgtcagcggg tgttggcggg tgtcggggct ggcttaacta 7740 tgcggcatca gagcagattg tactgagagt gcaccataaa attgtaaacg ttaatatttt 7800 gttaaaattc gcgttaaatt tttgttaaat cagctcattt tttaaccaat aggccgaaat 7860 cggcaaaatc ccttataaat caaaagaata gcccgagata gggttgagtg ttgttccagt 7920 ttggaacaag agtccactat taaagaacgt ggactccaac gtcaaagggc gaaaaaccgt 7980 ctatcagggc gatggcccac tacgtgaacc atcacccaaa tcaagttttt tggggtcgag 8040 gtgccgtaaa gcactaaatc ggaaccctaa agggagcccc cgatttagag cttgacgggg 8100 aaagccggcg aacgtggcga gaaaggaagg gaagaaagcg aaaggagcgg gcgctagggc 8160 gctggcaagt gtagcggtca cgctgcgcgt aaccaccaca cccgccgcgc ttaatgcgcc 8220 gctacagggc gcgtactatg gttgctttga cgtatgcggt gtgaaatacc gcacagatgc 8280 gtaaggagaa aataccgcat caggcgccat tcgccattca ggctgcgcaa ctgttgggaa 8340 gggcgatcgg tgcgggcctc ttcgctatta cgccagctgg cgaaaggggg atgtgctgca 8400 aggcgattaa gttgggtaac gccagggttt tcccagtcac gacgttgtaa aacgacggcc 8460 agtgaattcc atggtctcaa ctttc 8485 <210> 27 <211> 3831 <212> DNA <213> Artificial <220> <223> VLP74_11 (CHI VLP 532 NPNAx6) CHIKV-NPNAx6 sequence only <400> 27 atggagttca tcccgacgca aactttctat aacagaaggt accaaccccg accctgggcc 60 ccacgcccta caattcaagt aattagacct agaccacgtc cacagaggca ggctgggcaa 120 ctcgcccagc tgatctccgc agtcaacaaa ttgaccatgc gcgcggtacc tcaacagaag 180 cctcgcagaa atcggaaaaa caagaagcaa aggcagaaga agcaggcgcc gcaaaacgac 240 ccaaagcaaa agaagcaacc accacaaaag aagccggctc aaaagaagaa gaaaccaggc 300 cgtagggaga gaatgtgcat gaaaattgaa aatgattgca tcttcgaagt caagcatgaa 360 ggcaaagtga tgggctacgc atgcctggtg ggggataaag taatgaaacc agcacatgtg 420 aagggaacta tcgacaatgc cgatctggct aaactggcct ttaagcggtc gtctaaatac 480 gatcttgaat gtgcacagat accggtgcac atgaagtctg atgcctcgaa gtttacccac 540 gagaaacccg aggggtacta taactggcat cacggagcag tgcagtattc aggaggccgg 600 ttcactatcc cgacgggtgc aggcaagccg ggagacagcg gcagaccgat cttcgacaac 660 aaaggacggg tggtggccat cgtcctagga ggggccaacg aaggtgcccg cacggccctc 720 tccgtggtga cgtggaacaa agacatcgtc acaaaaatta cccctgaggg agccgaagag 780 tggagcctcg ccctcccggt cttgtgcctg ttggcaaaca ctacattccc ctgctctcag 840 ccgccttgca caccctgctg ctacgaaaag gaaccggaaa gcaccttgcg catgcttgag 900 gacaacgtga tgagacccgg atactaccag ctactaaaag catcgctgac ttgctctccc 960 caccgccaaa gacgcagtac taaggacaat tttaatgtct ataaagccac aagaccatat 1020 ctagctcatt gtcctgactg cggagaaggg cattcgtgcc acagccctat cgcattggag 1080 cgcatcagaa atgaagcaac ggacggaacg ctgaaaatcc aggtctcttt gcagatcggg 1140 ataaagacag atgacagcca cgattggacc aagctgcgct atatggatag ccatacgcca 1200 gcggacgcgg agcgagccgg attgcttgta aggacttcag caccgtgcac gatcaccggg 1260 accatgggac actttattct cgcccgatgc ccgaaaggag agacgctgac agtgggattt 1320 acggacagca gaaagatcag ccacacatgc acacacccgt tccatcatga accacctgtg 1380 ataggtaggg agaggttcca ctctcgacca caacatggta aagagttacc ttgcagcacg 1440 tacgtgcaga gcaccgctgc cactgctgag gagatagagg tgcatatgcc cccagatact 1500 cctgaccgca cgctgatgac gcagcagtct ggcaacgtga agatcacagt taatgggcag 1560 acggtgcggt acaagtgcaa ctgcggtggc tccggaggaa acccgaatgc caatcccaac 1620 gcgaacccca atgctaaccc aaatgccaac ccaaacgcca accccaacgc tggtggatcc 1680 aacgagggac tgacaaccac agacaaagtg atcaataact gcaaaattga tcagtgccat 1740 gctgcagtca ctaatcacaa gaattggcaa tacaactccc ctttagtccc gcgcaacgct 1800 gaactcgggg accgtaaagg aaagatccac atcccattcc cattggcaaa cgtgacttgc 1860 agagtgccaa aagcaagaaa ccctacagta acttacggaa aaaaccaagt caccatgctg 1920 ctgtatcctg accatccgac actcttgtct taccgtaaca tgggacagga accaaattac 1980 cacgaggagt gggtgacaca caagaaggag gttaccttga ccgtgcctac tgagggtctg 2040 gaggtcactt ggggcaacaa cgaaccatac aagtactggc cgcagatgtc tacgaacggt 2100 actgctcatg gtcacccaca tgagataatc ttgtactatt atgagctgta ccccactatg 2160 actgtagtca ttgtgtcggt ggcctcgttc gtgcttctgt cgatggtggg cacagcagtg 2220 ggaatgtgtg tgtgcgcacg gcgcagatgc attacaccat atgaattaac accaggagcc 2280 actgttccct tcctgctcag cctgctatgc tgcgtcagaa cgaccaaggc ggccacatat 2340 tacgaggctg cggcatatct atggaacgaa cagcagcccc tgttctggtt gcaggctctt 2400 atcccgctgg ccgccttgat cgtcctgtgc aactgtctga aactcttgcc atgctgctgt 2460 aagaccctgg cttttttagc cgtaatgagc atcggtgccc acactgtgag cgcgtacgaa 2520 cacgtaacag tgatcccgaa cacggtggga gtaccgtata agactcttgt caacagaccg 2580 ggttacagcc ccatggtgtt ggagatggag ctacaatcag tcaccttgga accaacactg 2640 tcacttgact acatcacgtg cgagtacaaa actgtcatcc cctccccgta cgtgaagtgc 2700 tgtggtacag cagagtgcaa ggacaagagc ctaccagact acagctgcaa ggtctttact 2760 ggagtctacc catttatgtg gggcggcgcc tactgctttt gcgacgccga aaatacgcaa 2820 ttgagcgagg cacatgtaga gaaatctgaa tcttgcaaaa cagagtttgc atcggcctac 2880 agagcccaca ccgcatcggc gtcggcgaag ctccgcgtcc tttaccaagg aaacaacatt 2940 accgtagctg cctacgctaa cggtgaccat gccgtcacag taaaggacgc caagtttgtc 3000 gtgggcccaa tgtcctccgc ctggacacct tttgacaaca aaatcgtggt gtacaaaggc 3060 gacgtctaca acatggacta cccacctttt ggcgcaggaa gaccaggaca atttggtgac 3120 attcaaagtc gtacaccgga aagtaaagac gtttatgcca acactcagtt ggtactacag 3180 aggccagcag caggcacggt acatgtacca tactctcagg caccatctgg cttcaagtat 3240 tggctgaagg aacgaggagc atcgctacag cacacggcac cgttcggttg ccagattgcg 3300 acaaacccgg taagagctgt aaattgcgct gtggggaaca taccaatttc catcgacata 3360 ccggatgcgg cctttactag ggttgtcgat gcaccctctg taacggacat gtcatgcgaa 3420 gtaccagcct gcactcactc ctccgacttt gggggcgtcg ccatcatcaa atacacagct 3480 agcaagaaag gtaaatgtgc agtacattcg atgaccaacg ccgttaccat tcgagaagcc 3540 gacgtagaag tagaggggaa ctcccagctg caaatatcct tctcaacagc cctggcaagc 3600 gccgagtttc gcgtgcaagt gtgctccaca caagtacact gcgcagccgc atgccaccct 3660 ccaaaggacc acatagtcaa ttacccagca tcacacacca cccttggggt ccaggatata 3720 tccacaacgg caatgtcttg ggtgcagaag attacgggag gagtaggatt aattgttgct 3780 gttgctgcct taattttaat tgtggtgcta tgcgtgtcgt ttagcaggca c 3831 <210> 28 <211> 1277 <212> PRT <213> Artificial <220> <223> VLP74_11 (CHI VLP 532 NPNAx6) amino acid sequence <400> 28 Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro 1 5 10 15 Arg Pro Trp Ala Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30 Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45 Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60 Arg Lys Asn Lys Lys Gln Arg Gln Lys Lys Gln Ala Pro Gln Asn Asp 65 70 75 80 Pro Lys Gln Lys Lys Gln Pro Pro Gln Lys Lys Pro Ala Gln Lys Lys 85 90 95 Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110 Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Met Gly Tyr Ala Cys 115 120 125 Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140 Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr 145 150 155 160 Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175 Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190 Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205 Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220 Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu 225 230 235 240 Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255 Gly Ala Glu Glu Trp Ser Leu Ala Leu Pro Val Leu Cys Leu Leu Ala 260 265 270 Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285 Glu Lys Glu Pro Glu Ser Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300 Arg Pro Gly Tyr Tyr Gln Leu Leu Lys Ala Ser Leu Thr Cys Ser Pro 305 310 315 320 His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335 Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350 Cys His Ser Pro Ile Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365 Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380 Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Ser His Thr Pro 385 390 395 400 Ala Asp Ala Glu Arg Ala Gly Leu Leu Val Arg Thr Ser Ala Pro Cys 405 410 415 Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430 Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445 Thr Cys Thr His Pro Phe His His Glu Pro Pro Val Ile Gly Arg Glu 450 455 460 Arg Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr 465 470 475 480 Tyr Val Gln Ser Thr Ala Ala Thr Ala Glu Glu Ile Glu Val His Met 485 490 495 Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Thr Gln Gln Ser Gly Asn 500 505 510 Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525 Gly Gly Ser Gly Gly Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 530 535 540 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Gly Gly Ser 545 550 555 560 Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Ile 565 570 575 Asp Gln Cys His Ala Ala Val Thr Asn His Lys Asn Trp Gln Tyr Asn 580 585 590 Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys 595 600 605 Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys 610 615 620 Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val Thr Met Leu 625 630 635 640 Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Gln 645 650 655 Glu Pro Asn Tyr His Glu Glu Trp Val Thr His Lys Lys Glu Val Thr 660 665 670 Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu 675 680 685 Pro Tyr Lys Tyr Trp Pro Gln Met Ser Thr Asn Gly Thr Ala His Gly 690 695 700 His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met 705 710 715 720 Thr Val Val Ile Val Ser Val Ala Ser Phe Val Leu Leu Ser Met Val 725 730 735 Gly Thr Ala Val Gly Met Cys Val Cys Ala Arg Arg Arg Cys Ile Thr 740 745 750 Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu Leu Ser Leu 755 760 765 Leu Cys Cys Val Arg Thr Thr Lys Ala Ala Thr Tyr Tyr Glu Ala Ala 770 775 780 Ala Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu Gln Ala Leu 785 790 795 800 Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu Lys Leu Leu 805 810 815 Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met Ser Ile Gly 820 825 830 Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile Pro Asn Thr 835 840 845 Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly Tyr Ser Pro 850 855 860 Met Val Leu Glu Met Glu Leu Gln Ser Val Thr Leu Glu Pro Thr Leu 865 870 875 880 Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile Pro Ser Pro 885 890 895 Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys Ser Leu Pro 900 905 910 Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe Met Trp Gly 915 920 925 Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu Ser Glu Ala 930 935 940 His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala Ser Ala Tyr 945 950 955 960 Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val Leu Tyr Gln 965 970 975 Gly Asn Asn Ile Thr Val Ala Ala Tyr Ala Asn Gly Asp His Ala Val 980 985 990 Thr Val Lys Asp Ala Lys Phe Val Val Gly Pro Met Ser Ser Ala Trp 995 1000 1005 Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp Val Tyr 1010 1015 1020 Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln Phe 1025 1030 1035 Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr Ala 1040 1045 1050 Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Ala Gly Thr Val His 1055 1060 1065 Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu Lys 1070 1075 1080 Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys Gln 1085 1090 1095 Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly Asn 1100 1105 1110 Ile Pro Ile Ser Ile Asp Ile Pro Asp Ala Ala Phe Thr Arg Val 1115 1120 1125 Val Asp Ala Pro Ser Val Thr Asp Met Ser Cys Glu Val Pro Ala 1130 1135 1140 Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys Tyr 1145 1150 1155 Thr Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr Asn 1160 1165 1170 Ala Val Thr Ile Arg Glu Ala Asp Val Glu Val Glu Gly Asn Ser 1175 1180 1185 Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu Phe 1190 1195 1200 Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Ala Cys 1205 1210 1215 His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His Thr 1220 1225 1230 Thr Leu Gly Val Gln Asp Ile Ser Thr Thr Ala Met Ser Trp Val 1235 1240 1245 Gln Lys Ile Thr Gly Gly Val Gly Leu Ile Val Ala Val Ala Ala 1250 1255 1260 Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1265 1270 1275 <210> 29 <211> 8713 <212> DNA <213> Artificial <220> <223> VLP78_11 (CHI VLP 532 NPNAx25) whole sequence <400> 29 gaattcccat tgcatacgtt gtatccatat cataatatgt acatttatat tggctcatgt 60 ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta atcaattacg 120 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 180 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 240 atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 300 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 360 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 420 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 480 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 540 gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 600 tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 660 gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt tgacctccat 720 agaagacacc gggaccgatc cagcctccgt taacggtgga gggcagtgta gtctgagcag 780 tactcgttgc tgccgcgcgc gccaccagac ataatagctg acagactaac agactgttcc 840 tttccatggg tcttttctgc agtcaccgtc gtcgacacgt gtgatcagat atcgcggccg 900 ccaccatgga gttcatcccg acgcaaactt tctataacag aaggtaccaa ccccgaccct 960 gggccccacg ccctacaatt caagtaatta gacctagacc acgtccacag aggcaggctg 1020 ggcaactcgc ccagctgatc tccgcagtca acaaattgac catgcgcgcg gtacctcaac 1080 agaagcctcg cagaaatcgg aaaaacaaga agcaaaggca gaagaagcag gcgccgcaaa 1140 acgacccaaa gcaaaagaag caaccaccac aaaagaagcc ggctcaaaag aagaagaaac 1200 caggccgtag ggagagaatg tgcatgaaaa ttgaaaatga ttgcatcttc gaagtcaagc 1260 atgaaggcaa agtgatgggc tacgcatgcc tggtggggga taaagtaatg aaaccagcac 1320 atgtgaaggg aactatcgac aatgccgatc tggctaaact ggcctttaag cggtcgtcta 1380 aatacgatct tgaatgtgca cagataccgg tgcacatgaa gtctgatgcc tcgaagttta 1440 cccacgagaa acccgagggg tactataact ggcatcacgg agcagtgcag tattcaggag 1500 gccggttcac tatcccgacg ggtgcaggca agccgggaga cagcggcaga ccgatcttcg 1560 acaacaaagg acgggtggtg gccatcgtcc taggaggggc caacgaaggt gcccgcacgg 1620 ccctctccgt ggtgacgtgg aacaaagaca tcgtcacaaa aattacccct gagggagccg 1680 aagagtggag cctcgccctc ccggtcttgt gcctgttggc aaacactaca ttcccctgct 1740 ctcagccgcc ttgcacaccc tgctgctacg aaaaggaacc ggaaagcacc ttgcgcatgc 1800 ttgaggacaa cgtgatgaga cccggatact accagctact aaaagcatcg ctgacttgct 1860 ctccccaccg ccaaagacgc agtactaagg acaattttaa tgtctataaa gccacaagac 1920 catatctagc tcattgtcct gactgcggag aagggcattc gtgccacagc cctatcgcat 1980 tggagcgcat cagaaatgaa gcaacggacg gaacgctgaa aatccaggtc tctttgcaga 2040 tcgggataaa gacagatgac agccacgatt ggaccaagct gcgctatatg gatagccata 2100 cgccagcgga cgcggagcga gccggattgc ttgtaaggac ttcagcaccg tgcacgatca 2160 ccgggaccat gggacacttt attctcgccc gatgcccgaa aggagagacg ctgacagtgg 2220 gatttacgga cagcagaaag atcagccaca catgcacaca cccgttccat catgaaccac 2280 ctgtgatagg tagggagagg ttccactctc gaccacaaca tggtaaagag ttaccttgca 2340 gcacgtacgt gcagagcacc gctgccactg ctgaggagat agaggtgcat atgcccccag 2400 atactcctga ccgcacgctg atgacgcagc agtctggcaa cgtgaagatc acagttaatg 2460 ggcagacggt gcggtacaag tgcaactgcg gtggctccgg aggaaacccg aatgccaatc 2520 ccaacgcgaa ccccaacgct aaccccaacg ccaatccgaa tgcaaacccg aacgttgacc 2580 caaacgccaa cccgaatgcc aatcccaacg cgaaccccaa tgctaaccca aatgccaacc 2640 caaacgccaa ccccaacgct aatccaaacg ccaaccctaa cgccaatccc aacgcgaatc 2700 ctaacgctaa tcccaacgca aatcccaatg ctaatccgaa cgcgaaccct aatgcaaacc 2760 ccaacgccaa cccgaacgct aacccgaacg ctaatcccaa cgccggtgga tccaacgagg 2820 gactgacaac cacagacaaa gtgatcaata actgcaaaat tgatcagtgc catgctgcag 2880 tcactaatca caagaattgg caatacaact cccctttagt cccgcgcaac gctgaactcg 2940 gggaccgtaa aggaaagatc cacatcccat tcccattggc aaacgtgact tgcagagtgc 3000 caaaagcaag aaaccctaca gtaacttacg gaaaaaacca agtcaccatg ctgctgtatc 3060 ctgaccatcc gacactcttg tcttaccgta acatgggaca ggaaccaaat taccacgagg 3120 agtgggtgac acacaagaag gaggttacct tgaccgtgcc tactgagggt ctggaggtca 3180 cttggggcaa caacgaacca tacaagtact ggccgcagat gtctacgaac ggtactgctc 3240 atggtcaccc acatgagata atcttgtact attatgagct gtaccccact atgactgtag 3300 tcattgtgtc ggtggcctcg ttcgtgcttc tgtcgatggt gggcacagca gtgggaatgt 3360 gtgtgtgcgc acggcgcaga tgcattacac catatgaatt aacaccagga gccactgttc 3420 ccttcctgct cagcctgcta tgctgcgtca gaacgaccaa ggcggccaca tattacgagg 3480 ctgcggcata tctatggaac gaacagcagc ccctgttctg gttgcaggct cttatcccgc 3540 tggccgcctt gatcgtcctg tgcaactgtc tgaaactctt gccatgctgc tgtaagaccc 3600 tggctttttt agccgtaatg agcatcggtg cccacactgt gagcgcgtac gaacacgtaa 3660 cagtgatccc gaacacggtg ggagtaccgt ataagactct tgtcaacaga ccgggttaca 3720 gccccatggt gttggagatg gagctacaat cagtcacctt ggaaccaaca ctgtcacttg 3780 actacatcac gtgcgagtac aaaactgtca tcccctcccc gtacgtgaag tgctgtggta 3840 cagcagagtg caaggacaag agcctaccag actacagctg caaggtcttt actggagtct 3900 acccatttat gtggggcggc gcctactgct tttgcgacgc cgaaaatacg caattgagcg 3960 aggcacatgt agagaaatct gaatcttgca aaacagagtt tgcatcggcc tacagagccc 4020 acaccgcatc ggcgtcggcg aagctccgcg tcctttacca aggaaacaac attaccgtag 4080 ctgcctacgc taacggtgac catgccgtca cagtaaagga cgccaagttt gtcgtgggcc 4140 caatgtcctc cgcctggaca ccttttgaca acaaaatcgt ggtgtacaaa ggcgacgtct 4200 acaacatgga ctacccacct tttggcgcag gaagaccagg acaatttggt gacattcaaa 4260 gtcgtacacc ggaaagtaaa gacgtttatg ccaacactca gttggtacta cagaggccag 4320 cagcaggcac ggtacatgta ccatactctc aggcaccatc tggcttcaag tattggctga 4380 aggaacgagg agcatcgcta cagcacacgg caccgttcgg ttgccagatt gcgacaaacc 4440 cggtaagagc tgtaaattgc gctgtgggga acataccaat ttccatcgac ataccggatg 4500 cggcctttac tagggttgtc gatgcaccct ctgtaacgga catgtcatgc gaagtaccag 4560 cctgcactca ctcctccgac tttgggggcg tcgccatcat caaatacaca gctagcaaga 4620 aaggtaaatg tgcagtacat tcgatgacca acgccgttac cattcgagaa gccgacgtag 4680 aagtagaggg gaactcccag ctgcaaatat ccttctcaac agccctggca agcgccgagt 4740 ttcgcgtgca agtgtgctcc acacaagtac actgcgcagc cgcatgccac cctccaaagg 4800 accacatagt caattaccca gcatcacaca ccacccttgg ggtccaggat atatccacaa 4860 cggcaatgtc ttgggtgcag aagattacgg gaggagtagg attaattgtt gctgttgctg 4920 ccttaatttt aattgtggtg ctatgcgtgt cgtttagcag gcactaagga tctagatctg 4980 ctgtgccttc tagttgccag ccatctgttg tttgcccctc ccccgtgcct tccttgaccc 5040 tggaaggtgc cactcccact gtcctttcct aataaaatga ggaaattgca tcgcattgtc 5100 tgagtaggtg tcattctatt ctggggggtg gggtggggca ggacagcaag ggggaggatt 5160 gggaagacaa tagcaggcat gctggggatg cggtgggctc tatgggtacc caggtgctga 5220 agaattgacc cggttcctcc tgggccagaa agaagcaggc acatcccctt ctctgtgaca 5280 caccctgtcc acgcccctgg ttcttagttc cagccccact cataggacac tcatagctca 5340 ggagggctcc gccttcaatc ccacccgcta aagtacttgg agcggtctct ccctccctca 5400 tcagcccacc aaaccaaacc tagcctccaa gagtgggaag aaattaaagc aagataggct 5460 attaagtgca gagggagaga aaatgcctcc aacatgtgag gaagtaatga gagaaatcat 5520 agaattttaa ggccatgatt taaggccatc atggcctaag cttgaaagga gataggatca 5580 aagcttggcg taatcatggt catagctgtt tcctgtgtga aattgttatc cgctcacaat 5640 tccacacaac atacgagccg gaagcataaa gtgtaaagcc tggggtgcct aatgagtgag 5700 ctaactcaca ttaattgcgt tgcgctcact gcccgctttc cagtcgggaa acctgtcgtg 5760 ccagctgcat taatgaatcg gccaacgcgc ggggagaggc ggtttgcgta ttgggcgctc 5820 ttccgcttcc tcgctcactg actcgctgcg ctcggtcgtt cggctgcggc gagcggtatc 5880 agctcactca aaggcggtaa tacggttatc cacagaatca ggggataacg caggaaagaa 5940 catgtgagca aaaggccagc aaaaggccag gaaccgtaaa aaggccgcgt tgctggcgtt 6000 tttccatagg ctccgccccc ctgacgagca tcacaaaaat cgacgctcaa gtcagaggtg 6060 gcgaaacccg acaggactat aaagatacca ggcgtttccc cctggaagct ccctcgtgcg 6120 ctctcctgtt ccgaccctgc cgcttaccgg atacctgtcc gcctttctcc cttcgggaag 6180 cgtggcgctt tctcatagct cacgctgtag gtatctcagt tcggtgtagg tcgttcgctc 6240 caagctgggc tgtgtgcacg aaccccccgt tcagcccgac cgctgcgcct tatccggtaa 6300 ctatcgtctt gagtccaacc cggtaagaca cgacttatcg ccactggcag cagccactgg 6360 taacaggatt agcagagcga ggtatgtagg cggtgctaca gagttcttga agtggtggcc 6420 taactacggc tacactagaa gaacagtatt tggtatctgc gctctgctga agccagttac 6480 cttcggaaaa agagttggta gctcttgatc cggcaaacaa accaccgctg gtagcggtgg 6540 tttttttgtt tgcaagcagc agattacgcg cagaaaaaaa ggatctcaag aagatccttt 6600 gatcttttct acggggtctg acgctcagtg gaacgaaaac tcacgttaag ggattttggt 6660 catgagatta tcaaaaagga tcttcaccta gatcctttta aattaaaaat gaagttttaa 6720 atcaatctaa agtatatatg agtaaacttg gtctgacagt taccaatgct taatcagtga 6780 ggcacctatc tcagcgatct gtctatttcg ttcatccata gttgcctgac tccccgtcgt 6840 gtagataact acgatacggg agggcttacc atctggcccc agtgctgcaa tgataccgcg 6900 agaaccacgc tcaccggctc cagatttatc agcaataaac cagccagccg gaagggccga 6960 gcgcagaagt ggtcctgcaa ctttatccgc ctccatccag tctattaatt gttgccggga 7020 agctagagta agtagttcgc cagttaatag tttgcgcaac gttgttgcca ttgctacagg 7080 catcgtggtg tcacgctcgt cgtttggtat ggcttcattc agctccggtt cccaacgatc 7140 aaggcgagtt acatgatccc ccatgttgtg caaaaaagcg gttagctcct tcggtcctcc 7200 gatcgttgtc agaagtaagt tggccgcagt gttatcactc atggttatgg cagcactgca 7260 taattctctt actgtcatgc catccgtaag atgcttttct gtgactggtg agtactcaac 7320 caagtcattc tgagaatagt gtatgcggcg accgagttgc tcttgcccgg cgtcaatacg 7380 ggataatacc gcgccacata gcagaacttt aaaagtgctc atcattggaa aacgttcttc 7440 ggggcgaaaa ctctcaagga tcttaccgct gttgagatcc agttcgatgt aacccactcg 7500 tgcacccaac tgatcttcag catcttttac tttcaccagc gtttctgggt gagcaaaaac 7560 aggaaggcaa aatgccgcaa aaaagggaat aagggcgaca cggaaatgtt gaatactcat 7620 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 7680 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 7740 agtgccacct gacgtctaag aaaccattat tatcatgaca ttaacctata aaaataggcg 7800 tatcacgagg ccctttcggg tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat 7860 gcagctcccg ttgacggtca cagcttgtct gtaagcggat gccgggagca gacaagcccg 7920 tcagggcgcg tcagcgggtg ttggcgggtg tcggggctgg cttaactatg cggcatcaga 7980 gcagattgta ctgagagtgc accataaaat tgtaaacgtt aatattttgt taaaattcgc 8040 gttaaatttt tgttaaatca gctcattttt taaccaatag gccgaaatcg gcaaaatccc 8100 ttataaatca aaagaatagc ccgagatagg gttgagtgtt gttccagttt ggaacaagag 8160 tccactatta aagaacgtgg actccaacgt caaagggcga aaaaccgtct atcagggcga 8220 tggcccacta cgtgaaccat cacccaaatc aagttttttg gggtcgaggt gccgtaaagc 8280 actaaatcgg aaccctaaag ggagcccccg atttagagct tgacggggaa agccggcgaa 8340 cgtggcgaga aaggaaggga agaaagcgaa aggagcgggc gctagggcgc tggcaagtgt 8400 agcggtcacg ctgcgcgtaa ccaccacacc cgccgcgctt aatgcgccgc tacagggcgc 8460 gtactatggt tgctttgacg tatgcggtgt gaaataccgc acagatgcgt aaggagaaaa 8520 taccgcatca ggcgccattc gccattcagg ctgcgcaact gttgggaagg gcgatcggtg 8580 cgggcctctt cgctattacg ccagctggcg aaagggggat gtgctgcaag gcgattaagt 8640 tgggtaacgc cagggttttc ccagtcacga cgttgtaaaa cgacggccag tgaattccat 8700 ggtctcaact ttc 8713 <210> 30 <211> 4059 <212> DNA <213> Artificial <220> <223> VLP78_11 (CHI VLP 532 NPNAx25) CHIKV-NPNAx25 sequence only <400> 30 atggagttca tcccgacgca aactttctat aacagaaggt accaaccccg accctgggcc 60 ccacgcccta caattcaagt aattagacct agaccacgtc cacagaggca ggctgggcaa 120 ctcgcccagc tgatctccgc agtcaacaaa ttgaccatgc gcgcggtacc tcaacagaag 180 cctcgcagaa atcggaaaaa caagaagcaa aggcagaaga agcaggcgcc gcaaaacgac 240 ccaaagcaaa agaagcaacc accacaaaag aagccggctc aaaagaagaa gaaaccaggc 300 cgtagggaga gaatgtgcat gaaaattgaa aatgattgca tcttcgaagt caagcatgaa 360 ggcaaagtga tgggctacgc atgcctggtg ggggataaag taatgaaacc agcacatgtg 420 aagggaacta tcgacaatgc cgatctggct aaactggcct ttaagcggtc gtctaaatac 480 gatcttgaat gtgcacagat accggtgcac atgaagtctg atgcctcgaa gtttacccac 540 gagaaacccg aggggtacta taactggcat cacggagcag tgcagtattc aggaggccgg 600 ttcactatcc cgacgggtgc aggcaagccg ggagacagcg gcagaccgat cttcgacaac 660 aaaggacggg tggtggccat cgtcctagga ggggccaacg aaggtgcccg cacggccctc 720 tccgtggtga cgtggaacaa agacatcgtc acaaaaatta cccctgaggg agccgaagag 780 tggagcctcg ccctcccggt cttgtgcctg ttggcaaaca ctacattccc ctgctctcag 840 ccgccttgca caccctgctg ctacgaaaag gaaccggaaa gcaccttgcg catgcttgag 900 gacaacgtga tgagacccgg atactaccag ctactaaaag catcgctgac ttgctctccc 960 caccgccaaa gacgcagtac taaggacaat tttaatgtct ataaagccac aagaccatat 1020 ctagctcatt gtcctgactg cggagaaggg cattcgtgcc acagccctat cgcattggag 1080 cgcatcagaa atgaagcaac ggacggaacg ctgaaaatcc aggtctcttt gcagatcggg 1140 ataaagacag atgacagcca cgattggacc aagctgcgct atatggatag ccatacgcca 1200 gcggacgcgg agcgagccgg attgcttgta aggacttcag caccgtgcac gatcaccggg 1260 accatgggac actttattct cgcccgatgc ccgaaaggag agacgctgac agtgggattt 1320 acggacagca gaaagatcag ccacacatgc acacacccgt tccatcatga accacctgtg 1380 ataggtaggg agaggttcca ctctcgacca caacatggta aagagttacc ttgcagcacg 1440 tacgtgcaga gcaccgctgc cactgctgag gagatagagg tgcatatgcc cccagatact 1500 cctgaccgca cgctgatgac gcagcagtct ggcaacgtga agatcacagt taatgggcag 1560 acggtgcggt acaagtgcaa ctgcggtggc tccggaggaa acccgaatgc caatcccaac 1620 gcgaacccca acgctaaccc caacgccaat ccgaatgcaa acccgaacgt tgacccaaac 1680 gccaacccga atgccaatcc caacgcgaac cccaatgcta acccaaatgc caacccaaac 1740 gccaacccca acgctaatcc aaacgccaac cctaacgcca atcccaacgc gaatcctaac 1800 gctaatccca acgcaaatcc caatgctaat ccgaacgcga accctaatgc aaaccccaac 1860 gccaacccga acgctaaccc gaacgctaat cccaacgccg gtggatccaa cgagggactg 1920 acaaccacag acaaagtgat caataactgc aaaattgatc agtgccatgc tgcagtcact 1980 aatcacaaga attggcaata caactcccct ttagtcccgc gcaacgctga actcggggac 2040 cgtaaaggaa agatccacat cccattccca ttggcaaacg tgacttgcag agtgccaaaa 2100 gcaagaaacc ctacagtaac ttacggaaaa aaccaagtca ccatgctgct gtatcctgac 2160 catccgacac tcttgtctta ccgtaacatg ggacaggaac caaattacca cgaggagtgg 2220 gtgacacaca agaaggaggt taccttgacc gtgcctactg agggtctgga ggtcacttgg 2280 ggcaacaacg aaccatacaa gtactggccg cagatgtcta cgaacggtac tgctcatggt 2340 cacccacatg agataatctt gtactattat gagctgtacc ccactatgac tgtagtcatt 2400 gtgtcggtgg cctcgttcgt gcttctgtcg atggtgggca cagcagtggg aatgtgtgtg 2460 tgcgcacggc gcagatgcat tacaccatat gaattaacac caggagccac tgttcccttc 2520 ctgctcagcc tgctatgctg cgtcagaacg accaaggcgg ccacatatta cgaggctgcg 2580 gcatatctat ggaacgaaca gcagcccctg ttctggttgc aggctcttat cccgctggcc 2640 gccttgatcg tcctgtgcaa ctgtctgaaa ctcttgccat gctgctgtaa gaccctggct 2700 tttttagccg taatgagcat cggtgcccac actgtgagcg cgtacgaaca cgtaacagtg 2760 atcccgaaca cggtgggagt accgtataag actcttgtca acagaccggg ttacagcccc 2820 atggtgttgg agatggagct acaatcagtc accttggaac caacactgtc acttgactac 2880 atcacgtgcg agtacaaaac tgtcatcccc tccccgtacg tgaagtgctg tggtacagca 2940 gagtgcaagg acaagagcct accagactac agctgcaagg tctttactgg agtctaccca 3000 tttatgtggg gcggcgccta ctgcttttgc gacgccgaaa atacgcaatt gagcgaggca 3060 catgtagaga aatctgaatc ttgcaaaaca gagtttgcat cggcctacag agcccacacc 3120 gcatcggcgt cggcgaagct ccgcgtcctt taccaaggaa acaacattac cgtagctgcc 3180 tacgctaacg gtgaccatgc cgtcacagta aaggacgcca agtttgtcgt gggcccaatg 3240 tcctccgcct ggacaccttt tgacaacaaa atcgtggtgt acaaaggcga cgtctacaac 3300 atggactacc caccttttgg cgcaggaaga ccaggacaat ttggtgacat tcaaagtcgt 3360 acaccggaaa gtaaagacgt ttatgccaac actcagttgg tactacagag gccagcagca 3420 ggcacggtac atgtaccata ctctcaggca ccatctggct tcaagtattg gctgaaggaa 3480 cgaggagcat cgctacagca cacggcaccg ttcggttgcc agattgcgac aaacccggta 3540 agagctgtaa attgcgctgt ggggaacata ccaatttcca tcgacatacc ggatgcggcc 3600 tttactaggg ttgtcgatgc accctctgta acggacatgt catgcgaagt accagcctgc 3660 actcactcct ccgactttgg gggcgtcgcc atcatcaaat acacagctag caagaaaggt 3720 aaatgtgcag tacattcgat gaccaacgcc gttaccattc gagaagccga cgtagaagta 3780 gaggggaact cccagctgca aatatccttc tcaacagccc tggcaagcgc cgagtttcgc 3840 gtgcaagtgt gctccacaca agtacactgc gcagccgcat gccaccctcc aaaggaccac 3900 atagtcaatt acccagcatc acacaccacc cttggggtcc aggatatatc cacaacggca 3960 atgtcttggg tgcagaagat tacgggagga gtaggattaa ttgttgctgt tgctgcctta 4020 attttaattg tggtgctatg cgtgtcgttt agcaggcac 4059 <210> 31 <211> 1353 <212> PRT <213> Artificial <220> <223> VLP78_11 (CHI VLP 532 NPNAx25) amino acid sequence <400> 31 Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro 1 5 10 15 Arg Pro Trp Ala Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30 Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45 Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60 Arg Lys Asn Lys Lys Gln Arg Gln Lys Lys Gln Ala Pro Gln Asn Asp 65 70 75 80 Pro Lys Gln Lys Lys Gln Pro Pro Gln Lys Lys Pro Ala Gln Lys Lys 85 90 95 Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110 Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Met Gly Tyr Ala Cys 115 120 125 Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140 Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr 145 150 155 160 Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175 Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190 Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205 Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220 Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu 225 230 235 240 Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255 Gly Ala Glu Glu Trp Ser Leu Ala Leu Pro Val Leu Cys Leu Leu Ala 260 265 270 Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285 Glu Lys Glu Pro Glu Ser Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300 Arg Pro Gly Tyr Tyr Gln Leu Leu Lys Ala Ser Leu Thr Cys Ser Pro 305 310 315 320 His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335 Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350 Cys His Ser Pro Ile Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365 Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380 Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Ser His Thr Pro 385 390 395 400 Ala Asp Ala Glu Arg Ala Gly Leu Leu Val Arg Thr Ser Ala Pro Cys 405 410 415 Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430 Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445 Thr Cys Thr His Pro Phe His His Glu Pro Pro Val Ile Gly Arg Glu 450 455 460 Arg Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr 465 470 475 480 Tyr Val Gln Ser Thr Ala Ala Thr Ala Glu Glu Ile Glu Val His Met 485 490 495 Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Thr Gln Gln Ser Gly Asn 500 505 510 Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525 Gly Gly Ser Gly Gly Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 530 535 540 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Val Asp Pro Asn 545 550 555 560 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 565 570 575 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 580 585 590 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 595 600 605 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 610 615 620 Ala Asn Pro Asn Ala Asn Pro Asn Ala Gly Gly Ser Asn Glu Gly Leu 625 630 635 640 Thr Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Ile Asp Gln Cys His 645 650 655 Ala Ala Val Thr Asn His Lys Asn Trp Gln Tyr Asn Ser Pro Leu Val 660 665 670 Pro Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile Pro 675 680 685 Phe Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn Pro 690 695 700 Thr Val Thr Tyr Gly Lys Asn Gln Val Thr Met Leu Leu Tyr Pro Asp 705 710 715 720 His Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Gln Glu Pro Asn Tyr 725 730 735 His Glu Glu Trp Val Thr His Lys Lys Glu Val Thr Leu Thr Val Pro 740 745 750 Thr Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys Tyr 755 760 765 Trp Pro Gln Met Ser Thr Asn Gly Thr Ala His Gly His Pro His Glu 770 775 780 Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr Val Val Ile 785 790 795 800 Val Ser Val Ala Ser Phe Val Leu Leu Ser Met Val Gly Thr Ala Val 805 810 815 Gly Met Cys Val Cys Ala Arg Arg Arg Cys Ile Thr Pro Tyr Glu Leu 820 825 830 Thr Pro Gly Ala Thr Val Pro Phe Leu Leu Ser Leu Leu Cys Cys Val 835 840 845 Arg Thr Thr Lys Ala Ala Thr Tyr Tyr Glu Ala Ala Ala Tyr Leu Trp 850 855 860 Asn Glu Gln Gln Pro Leu Phe Trp Leu Gln Ala Leu Ile Pro Leu Ala 865 870 875 880 Ala Leu Ile Val Leu Cys Asn Cys Leu Lys Leu Leu Pro Cys Cys Cys 885 890 895 Lys Thr Leu Ala Phe Leu Ala Val Met Ser Ile Gly Ala His Thr Val 900 905 910 Ser Ala Tyr Glu His Val Thr Val Ile Pro Asn Thr Val Gly Val Pro 915 920 925 Tyr Lys Thr Leu Val Asn Arg Pro Gly Tyr Ser Pro Met Val Leu Glu 930 935 940 Met Glu Leu Gln Ser Val Thr Leu Glu Pro Thr Leu Ser Leu Asp Tyr 945 950 955 960 Ile Thr Cys Glu Tyr Lys Thr Val Ile Pro Ser Pro Tyr Val Lys Cys 965 970 975 Cys Gly Thr Ala Glu Cys Lys Asp Lys Ser Leu Pro Asp Tyr Ser Cys 980 985 990 Lys Val Phe Thr Gly Val Tyr Pro Phe Met Trp Gly Gly Ala Tyr Cys 995 1000 1005 Phe Cys Asp Ala Glu Asn Thr Gln Leu Ser Glu Ala His Val Glu 1010 1015 1020 Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala Ser Ala Tyr Arg Ala 1025 1030 1035 His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val Leu Tyr Gln Gly 1040 1045 1050 Asn Asn Ile Thr Val Ala Ala Tyr Ala Asn Gly Asp His Ala Val 1055 1060 1065 Thr Val Lys Asp Ala Lys Phe Val Val Gly Pro Met Ser Ser Ala 1070 1075 1080 Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp Val 1085 1090 1095 Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 1100 1105 1110 Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1115 1120 1125 Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Ala Gly Thr Val 1130 1135 1140 His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1145 1150 1155 Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1160 1165 1170 Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly 1175 1180 1185 Asn Ile Pro Ile Ser Ile Asp Ile Pro Asp Ala Ala Phe Thr Arg 1190 1195 1200 Val Val Asp Ala Pro Ser Val Thr Asp Met Ser Cys Glu Val Pro 1205 1210 1215 Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1220 1225 1230 Tyr Thr Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1235 1240 1245 Asn Ala Val Thr Ile Arg Glu Ala Asp Val Glu Val Glu Gly Asn 1250 1255 1260 Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu 1265 1270 1275 Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Ala 1280 1285 1290 Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1295 1300 1305 Thr Thr Leu Gly Val Gln Asp Ile Ser Thr Thr Ala Met Ser Trp 1310 1315 1320 Val Gln Lys Ile Thr Gly Gly Val Gly Leu Ile Val Ala Val Ala 1325 1330 1335 Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1340 1345 1350 <210> 32 <211> 8737 <212> DNA <213> Artificial <220> <223> VLP78_21 (VEEV VLP 519 NPNAx25) whole sequence <400> 32 gaattcccat tgcatacgtt gtatccatat cataatatgt acatttatat tggctcatgt 60 ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta atcaattacg 120 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 180 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 240 atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 300 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 360 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 420 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 480 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 540 gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 600 tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 660 gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt tgacctccat 720 agaagacacc gggaccgatc cagcctccgt taacggtgga gggcagtgta gtctgagcag 780 tactcgttgc tgccgcgcgc gccaccagac ataatagctg acagactaac agactgttcc 840 tttccatggg tcttttctgc agtcaccgtc gtcgacacgt gtgatcagat atcgcggccg 900 ccaccatgtt cccgttccag ccaatgtatc cgatgcagcc aatgccctat cgcaacccgt 960 tcgcggcccc gcgcaggccc tggttcccca gaaccgaccc ttttctggcg atgcaggtgc 1020 aggaattaac ccgctcgatg gctaacctga cgttcaagca acgccgggac gcgccacctg 1080 aggggccatc cgctaataaa ccgaagaagg aggcctcgca aaaacagaaa gggggaggcc 1140 aagggaagaa gaagaagaac caagggaaga agaaggctaa gacagggccg cctaatccga 1200 aggcacagaa tggaaacaag aagaagacca acaagaaacc aggcaagaga cagcgcatgg 1260 tcatgaaatt ggaatctgac aagacgttcc caatcatgtt ggaagggaag ataaacggct 1320 acgcttgtgt ggtcggaggg aagttattca ggccgatgca tgtggaaggc aagatcgaca 1380 acgacgttct ggccgcgctt aagacgaaga aagcatccaa atacgatctt gagtatgcag 1440 atgtgccaca gaacatgcgg gccgatacat tcaaatacac ccatgagaaa ccccaaggct 1500 attacagctg gcatcatgga gcagtccaat atgaaaatgg gcgtttcacg gtgccgaaag 1560 gagttggggc caagggagac agcggacgac ccattctgga taaccaggga cgggtggtcg 1620 ctattgtgct gggaggtgtg aatgaaggat ctaggacagc cctttcagtc gtcatgtgga 1680 acgagaaggg agttaccgtg aagtatactc cagagaactg cgagcaatgg tcactagtga 1740 ccaccatgtg tctgctcgcc aatgtgacgt tcccatgtgc tcaaccacca atttgctacg 1800 acagaaaacc agcagagact ttggccatgc tcagcgttaa cgttgacaac ccgggctacg 1860 atgagctgct ggaagcagct gttaagtgcc ccggaaggaa aaggagatcc accgaggagc 1920 tgtttaatga gtataagcta acgcgccctt acatggccag atgcatcaga tgtgcagttg 1980 ggagctgcca tagtccaata gcaatcgagg cagtaaagag cgacgggcac gacggttatg 2040 ttagacttca gacttcctcg cagtatggcc tggattcctc cggcaactta aagggcagga 2100 ccatgcggta tgacatgcac gggaccatta aagagatacc actacatcaa gtgtcactct 2160 atacatctcg cccgtgtcac attgtggatg ggcacggtta tttcctgctt gccaggtgcc 2220 cggcagggga ctccatcacc atggaattta agaaagattc cgtcagacac tcctgctcgg 2280 tgccgtatga agtgaaattt aatcctgtag gcagagaact ctatactcat cccccagaac 2340 acggagtaga gcaagcgtgc caagtctacg cacatgatgc acagaacaga ggagcttatg 2400 tcgagatgca cctcccgggc tcagaagtgg acagcagttt ggtttccttg agcggcagtt 2460 ccggaggaaa cccgaatgcc aatcccaacg cgaaccccaa cgctaacccc aacgccaatc 2520 cgaatgcaaa cccgaacgtt gacccaaacg ccaacccgaa tgccaatccc aacgcgaacc 2580 ccaatgctaa cccaaatgcc aacccaaacg ccaaccccaa cgctaatcca aacgccaacc 2640 ctaacgccaa tcccaacgcg aatcctaacg ctaatcccaa cgcaaatccc aatgctaatc 2700 cgaacgcgaa ccctaatgca aaccccaacg ccaacccgaa cgctaacccg aacgctaatc 2760 ccaacgccgg tggatcctca gtcaccgtga cacctcctga tgggactagc gccctggtgg 2820 aatgcgagtg tggcggcaca aagatctccg agaccatcaa caagacaaaa cagttcagcc 2880 agtgcacaaa gaaggagcag tgcagagcat atcggctgca gaacgataag tgggtgtata 2940 attctgacaa actgcccaaa gcagcgggag ccaccttaaa aggaaaactg catgtcccat 3000 tcttgctggc agacggcaaa tgcaccgtgc ctctagcacc agaacctatg ataaccttcg 3060 gtttcagatc agtgtcactg aaactgcacc ctaagaatcc cacatatcta atcacccgcc 3120 aacttgctga tgagcctcac tacacgcacg agctcatatc tgaaccagct gttaggaatt 3180 ttaccgtcac cgaaaaaggg tgggagtttg tatggggaaa ccacccgccg aaaaggtttt 3240 gggcacagga aacagcaccc ggaaatccac atgggctacc gcacgaggtg ataactcatt 3300 attaccacag ataccctatg tccaccatcc tgggtttgtc aatttgtgcc gccattgcaa 3360 ccgtttccgt tgcagcgtct acctggctgt tttgcagatc aagagttgcg tgcctaactc 3420 cttaccggct aacacctaac gctaggatac cattttgtct ggctgtgctt tgctgcgccc 3480 gcactgcccg ggccgagacc acctgggagt ccttggatca cctatggaac aataaccaac 3540 agatgttctg gattcaattg ctgatccctc tggccgcctt gatcgtagtg actcgcctgc 3600 tcaggtgcgt gtgctgtgtc gtgccttttt tagtcatggc cggcgccgca ggcgccggcg 3660 cctacgagca cgcgaccacg atgccgagcc aagcgggaat ctcgtataac actatagtca 3720 acagagcagg ctacgcacca ctccctatca gcataacacc aacaaagatc aagctgatac 3780 ctacagtgaa cttggagtac gtcacctgcc actacaaaac aggaatggat tcaccagcca 3840 tcaaatgctg cggatctcag gaatgcactc caacttacag gcctgatgaa cagtgcaaag 3900 tcttcacagg ggtttacccg ttcatgtggg gtggtgcata ttgcttttgc gacactgaga 3960 acacccaagt cagcaaggcc tacgtaatga aatctgacga ctgccttgcg gatcatgctg 4020 aagcatataa agcgcacaca gcctcagtgc aggcgttcct caacatcaca gtgggagaac 4080 actctattgt gactaccgtg tatgtgaatg gagaaactcc tgtgaatttc aatggggtca 4140 aaataactgc aggtccgctt tccacagctt ggacaccctt tgatcgcaaa atcgtgcagt 4200 atgccgggga gatctataat tatgattttc ctgagtatgg ggcaggacaa ccaggagcat 4260 ttggagatat acaatccaga acagtctcaa gctctgatct gtatgccaat accaacctag 4320 tgctgcagag acccaaagca ggagcgatcc acgtgccata cactcaggca ccttcgggtt 4380 ttgagcaatg gaagaaagat aaagctccat cattgaaatt taccgcccct ttcggatgcg 4440 aaatatatac aaaccccatt cgcgccgaaa actgtgctgt agggtcaatt ccattagcct 4500 ttgacattcc cgacgccttg ttcaccaggg tgtcagaaac accgacactt tcagcggccg 4560 aatgcactct taacgagtgc gtgtattctt ccgactttgg tgggatcgcc acggtcaagt 4620 actcggccag caagtcaggc aagtgcgcag tccatgtgcc atcagggact gctaccctaa 4680 aagaagcagc agtcgagcta accgagcaag ggtcggcgac tatccatttc tcgaccgcaa 4740 atatccaccc ggagttcagg ctccaaatat gcacatcata tgttacgtgc aaaggtgatt 4800 gtcacccccc gaaagaccat attgtgacac accctcagta tcacgcccaa acatttacag 4860 ccgcggtgtc aaaaaccgcg tggacgtggt taacatccct gctgggagga tcagccgtaa 4920 ttattataat tggcttggtg ctggctacta ttgtggccat gtacgtgctg accaaccaga 4980 aacataatta aggatctaga tctgctgtgc cttctagttg ccagccatct gttgtttgcc 5040 cctcccccgt gccttccttg accctggaag gtgccactcc cactgtcctt tcctaataaa 5100 atgaggaaat tgcatcgcat tgtctgagta ggtgtcattc tattctgggg ggtggggtgg 5160 ggcaggacag caagggggag gattgggaag acaatagcag gcatgctggg gatgcggtgg 5220 gctctatggg tacccaggtg ctgaagaatt gacccggttc ctcctgggcc agaaagaagc 5280 aggcacatcc ccttctctgt gacacaccct gtccacgccc ctggttctta gttccagccc 5340 cactcatagg acactcatag ctcaggaggg ctccgccttc aatcccaccc gctaaagtac 5400 ttggagcggt ctctccctcc ctcatcagcc caccaaacca aacctagcct ccaagagtgg 5460 gaagaaatta aagcaagata ggctattaag tgcagaggga gagaaaatgc ctccaacatg 5520 tgaggaagta atgagagaaa tcatagaatt ttaaggccat gatttaaggc catcatggcc 5580 taagcttgaa aggagatagg atcaaagctt ggcgtaatca tggtcatagc tgtttcctgt 5640 gtgaaattgt tatccgctca caattccaca caacatacga gccggaagca taaagtgtaa 5700 agcctggggt gcctaatgag tgagctaact cacattaatt gcgttgcgct cactgcccgc 5760 tttccagtcg ggaaacctgt cgtgccagct gcattaatga atcggccaac gcgcggggag 5820 aggcggtttg cgtattgggc gctcttccgc ttcctcgctc actgactcgc tgcgctcggt 5880 cgttcggctg cggcgagcgg tatcagctca ctcaaaggcg gtaatacggt tatccacaga 5940 atcaggggat aacgcaggaa agaacatgtg agcaaaaggc cagcaaaagg ccaggaaccg 6000 taaaaaggcc gcgttgctgg cgtttttcca taggctccgc ccccctgacg agcatcacaa 6060 aaatcgacgc tcaagtcaga ggtggcgaaa cccgacagga ctataaagat accaggcgtt 6120 tccccctgga agctccctcg tgcgctctcc tgttccgacc ctgccgctta ccggatacct 6180 gtccgccttt ctcccttcgg gaagcgtggc gctttctcat agctcacgct gtaggtatct 6240 cagttcggtg taggtcgttc gctccaagct gggctgtgtg cacgaacccc ccgttcagcc 6300 cgaccgctgc gccttatccg gtaactatcg tcttgagtcc aacccggtaa gacacgactt 6360 atcgccactg gcagcagcca ctggtaacag gattagcaga gcgaggtatg taggcggtgc 6420 tacagagttc ttgaagtggt ggcctaacta cggctacact agaagaacag tatttggtat 6480 ctgcgctctg ctgaagccag ttaccttcgg aaaaagagtt ggtagctctt gatccggcaa 6540 acaaaccacc gctggtagcg gtggtttttt tgtttgcaag cagcagatta cgcgcagaaa 6600 aaaaggatct caagaagatc ctttgatctt ttctacgggg tctgacgctc agtggaacga 6660 aaactcacgt taagggattt tggtcatgag attatcaaaa aggatcttca cctagatcct 6720 tttaaattaa aaatgaagtt ttaaatcaat ctaaagtata tatgagtaaa cttggtctga 6780 cagttaccaa tgcttaatca gtgaggcacc tatctcagcg atctgtctat ttcgttcatc 6840 catagttgcc tgactccccg tcgtgtagat aactacgata cgggagggct taccatctgg 6900 ccccagtgct gcaatgatac cgcgagaacc acgctcaccg gctccagatt tatcagcaat 6960 aaaccagcca gccggaaggg ccgagcgcag aagtggtcct gcaactttat ccgcctccat 7020 ccagtctatt aattgttgcc gggaagctag agtaagtagt tcgccagtta atagtttgcg 7080 caacgttgtt gccattgcta caggcatcgt ggtgtcacgc tcgtcgtttg gtatggcttc 7140 attcagctcc ggttcccaac gatcaaggcg agttacatga tcccccatgt tgtgcaaaaa 7200 agcggttagc tccttcggtc ctccgatcgt tgtcagaagt aagttggccg cagtgttatc 7260 actcatggtt atggcagcac tgcataattc tcttactgtc atgccatccg taagatgctt 7320 ttctgtgact ggtgagtact caaccaagtc attctgagaa tagtgtatgc ggcgaccgag 7380 ttgctcttgc ccggcgtcaa tacgggataa taccgcgcca catagcagaa ctttaaaagt 7440 gctcatcatt ggaaaacgtt cttcggggcg aaaactctca aggatcttac cgctgttgag 7500 atccagttcg atgtaaccca ctcgtgcacc caactgatct tcagcatctt ttactttcac 7560 cagcgtttct gggtgagcaa aaacaggaag gcaaaatgcc gcaaaaaagg gaataagggc 7620 gacacggaaa tgttgaatac tcatactctt cctttttcaa tattattgaa gcatttatca 7680 gggttattgt ctcatgagcg gatacatatt tgaatgtatt tagaaaaata aacaaatagg 7740 ggttccgcgc acatttcccc gaaaagtgcc acctgacgtc taagaaacca ttattatcat 7800 gacattaacc tataaaaata ggcgtatcac gaggcccttt cgggtcgcgc gtttcggtga 7860 tgacggtgaa aacctctgac acatgcagct cccgttgacg gtcacagctt gtctgtaagc 7920 ggatgccggg agcagacaag cccgtcaggg cgcgtcagcg ggtgttggcg ggtgtcgggg 7980 ctggcttaac tatgcggcat cagagcagat tgtactgaga gtgcaccata aaattgtaaa 8040 cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa atcagctcat tttttaacca 8100 ataggccgaa atcggcaaaa tcccttataa atcaaaagaa tagcccgaga tagggttgag 8160 tgttgttcca gtttggaaca agagtccact attaaagaac gtggactcca acgtcaaagg 8220 gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa ccatcaccca aatcaagttt 8280 tttggggtcg aggtgccgta aagcactaaa tcggaaccct aaagggagcc cccgatttag 8340 agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa gggaagaaag cgaaaggagc 8400 gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc gtaaccacca cacccgccgc 8460 gcttaatgcg ccgctacagg gcgcgtacta tggttgcttt gacgtatgcg gtgtgaaata 8520 ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc attcgccatt caggctgcgc 8580 aactgttggg aagggcgatc ggtgcgggcc tcttcgctat tacgccagct ggcgaaaggg 8640 ggatgtgctg caaggcgatt aagttgggta acgccagggt tttcccagtc acgacgttgt 8700 aaaacgacgg ccagtgaatt ccatggtctc aactttc 8737 <210> 33 <211> 4086 <212> DNA <213> Artificial <220> <223> VLP78_21 (VEEV VLP 519 NPNAx25) VEEV-NPNAx25 sequence only <400> 33 atgttcccgt tccagccaat gtatccgatg cagccaatgc cctatcgcaa cccgttcgcg 60 gccccgcgca ggccctggtt ccccagaacc gacccttttc tggcgatgca ggtgcaggaa 120 ttaacccgct cgatggctaa cctgacgttc aagcaacgcc gggacgcgcc acctgagggg 180 ccatccgcta ataaaccgaa gaaggaggcc tcgcaaaaac agaaaggggg aggccaaggg 240 aagaagaaga agaaccaagg gaagaagaag gctaagacag ggccgcctaa tccgaaggca 300 cagaatggaa acaagaagaa gaccaacaag aaaccaggca agagacagcg catggtcatg 360 aaattggaat ctgacaagac gttcccaatc atgttggaag ggaagataaa cggctacgct 420 tgtgtggtcg gagggaagtt attcaggccg atgcatgtgg aaggcaagat cgacaacgac 480 gttctggccg cgcttaagac gaagaaagca tccaaatacg atcttgagta tgcagatgtg 540 ccacagaaca tgcgggccga tacattcaaa tacacccatg agaaacccca aggctattac 600 agctggcatc atggagcagt ccaatatgaa aatgggcgtt tcacggtgcc gaaaggagtt 660 ggggccaagg gagacagcgg acgacccatt ctggataacc agggacgggt ggtcgctatt 720 gtgctgggag gtgtgaatga aggatctagg acagcccttt cagtcgtcat gtggaacgag 780 aagggagtta ccgtgaagta tactccagag aactgcgagc aatggtcact agtgaccacc 840 atgtgtctgc tcgccaatgt gacgttccca tgtgctcaac caccaatttg ctacgacaga 900 aaaccagcag agactttggc catgctcagc gttaacgttg acaacccggg ctacgatgag 960 ctgctggaag cagctgttaa gtgccccgga aggaaaagga gatccaccga ggagctgttt 1020 aatgagtata agctaacgcg cccttacatg gccagatgca tcagatgtgc agttgggagc 1080 tgccatagtc caatagcaat cgaggcagta aagagcgacg ggcacgacgg ttatgttaga 1140 cttcagactt cctcgcagta tggcctggat tcctccggca acttaaaggg caggaccatg 1200 cggtatgaca tgcacgggac cattaaagag ataccactac atcaagtgtc actctataca 1260 tctcgcccgt gtcacattgt ggatgggcac ggttatttcc tgcttgccag gtgcccggca 1320 ggggactcca tcaccatgga atttaagaaa gattccgtca gacactcctg ctcggtgccg 1380 tatgaagtga aatttaatcc tgtaggcaga gaactctata ctcatccccc agaacacgga 1440 gtagagcaag cgtgccaagt ctacgcacat gatgcacaga acagaggagc ttatgtcgag 1500 atgcacctcc cgggctcaga agtggacagc agtttggttt ccttgagcgg cagttccgga 1560 ggaaacccga atgccaatcc caacgcgaac cccaacgcta accccaacgc caatccgaat 1620 gcaaacccga acgttgaccc aaacgccaac ccgaatgcca atcccaacgc gaaccccaat 1680 gctaacccaa atgccaaccc aaacgccaac cccaacgcta atccaaacgc caaccctaac 1740 gccaatccca acgcgaatcc taacgctaat cccaacgcaa atcccaatgc taatccgaac 1800 gcgaacccta atgcaaaccc caacgccaac ccgaacgcta acccgaacgc taatcccaac 1860 gccggtggat cctcagtcac cgtgacacct cctgatggga ctagcgccct ggtggaatgc 1920 gagtgtggcg gcacaaagat ctccgagacc atcaacaaga caaaacagtt cagccagtgc 1980 acaaagaagg agcagtgcag agcatatcgg ctgcagaacg ataagtgggt gtataattct 2040 gacaaactgc ccaaagcagc gggagccacc ttaaaaggaa aactgcatgt cccattcttg 2100 ctggcagacg gcaaatgcac cgtgcctcta gcaccagaac ctatgataac cttcggtttc 2160 agatcagtgt cactgaaact gcaccctaag aatcccacat atctaatcac ccgccaactt 2220 gctgatgagc ctcactacac gcacgagctc atatctgaac cagctgttag gaattttacc 2280 gtcaccgaaa aagggtggga gtttgtatgg ggaaaccacc cgccgaaaag gttttgggca 2340 caggaaacag cacccggaaa tccacatggg ctaccgcacg aggtgataac tcattattac 2400 cacagatacc ctatgtccac catcctgggt ttgtcaattt gtgccgccat tgcaaccgtt 2460 tccgttgcag cgtctacctg gctgttttgc agatcaagag ttgcgtgcct aactccttac 2520 cggctaacac ctaacgctag gataccattt tgtctggctg tgctttgctg cgcccgcact 2580 gcccgggccg agaccacctg ggagtccttg gatcacctat ggaacaataa ccaacagatg 2640 ttctggattc aattgctgat ccctctggcc gccttgatcg tagtgactcg cctgctcagg 2700 tgcgtgtgct gtgtcgtgcc ttttttagtc atggccggcg ccgcaggcgc cggcgcctac 2760 gagcacgcga ccacgatgcc gagccaagcg ggaatctcgt ataacactat agtcaacaga 2820 gcaggctacg caccactccc tatcagcata acaccaacaa agatcaagct gatacctaca 2880 gtgaacttgg agtacgtcac ctgccactac aaaacaggaa tggattcacc agccatcaaa 2940 tgctgcggat ctcaggaatg cactccaact tacaggcctg atgaacagtg caaagtcttc 3000 acaggggttt acccgttcat gtggggtggt gcatattgct tttgcgacac tgagaacacc 3060 caagtcagca aggcctacgt aatgaaatct gacgactgcc ttgcggatca tgctgaagca 3120 tataaagcgc acacagcctc agtgcaggcg ttcctcaaca tcacagtggg agaacactct 3180 attgtgacta ccgtgtatgt gaatggagaa actcctgtga atttcaatgg ggtcaaaata 3240 actgcaggtc cgctttccac agcttggaca ccctttgatc gcaaaatcgt gcagtatgcc 3300 ggggagatct ataattatga ttttcctgag tatggggcag gacaaccagg agcatttgga 3360 gatatacaat ccagaacagt ctcaagctct gatctgtatg ccaataccaa cctagtgctg 3420 cagagaccca aagcaggagc gatccacgtg ccatacactc aggcaccttc gggttttgag 3480 caatggaaga aagataaagc tccatcattg aaatttaccg cccctttcgg atgcgaaata 3540 tatacaaacc ccattcgcgc cgaaaactgt gctgtagggt caattccatt agcctttgac 3600 attcccgacg ccttgttcac cagggtgtca gaaacaccga cactttcagc ggccgaatgc 3660 actcttaacg agtgcgtgta ttcttccgac tttggtggga tcgccacggt caagtactcg 3720 gccagcaagt caggcaagtg cgcagtccat gtgccatcag ggactgctac cctaaaagaa 3780 gcagcagtcg agctaaccga gcaagggtcg gcgactatcc atttctcgac cgcaaatatc 3840 cacccggagt tcaggctcca aatatgcaca tcatatgtta cgtgcaaagg tgattgtcac 3900 cccccgaaag accatattgt gacacaccct cagtatcacg cccaaacatt tacagccgcg 3960 gtgtcaaaaa ccgcgtggac gtggttaaca tccctgctgg gaggatcagc cgtaattatt 4020 ataattggct tggtgctggc tactattgtg gccatgtacg tgctgaccaa ccagaaacat 4080 aattaa 4086 <210> 34 <211> 1361 <212> PRT <213> Artificial <220> <223> VLP78_21 (VEEV VLP 519 NPNAx25) amino acid sequence <400> 34 Met Phe Pro Phe Gln Pro Met Tyr Pro Met Gln Pro Met Pro Tyr Arg 1 5 10 15 Asn Pro Phe Ala Ala Pro Arg Arg Pro Trp Phe Pro Arg Thr Asp Pro 20 25 30 Phe Leu Ala Met Gln Val Gln Glu Leu Thr Arg Ser Met Ala Asn Leu 35 40 45 Thr Phe Lys Gln Arg Arg Asp Ala Pro Pro Glu Gly Pro Ser Ala Asn 50 55 60 Lys Pro Lys Lys Glu Ala Ser Gln Lys Gln Lys Gly Gly Gly Gln Gly 65 70 75 80 Lys Lys Lys Lys Asn Gln Gly Lys Lys Lys Ala Lys Thr Gly Pro Pro 85 90 95 Asn Pro Lys Ala Gln Asn Gly Asn Lys Lys Lys Thr Asn Lys Lys Pro 100 105 110 Gly Lys Arg Gln Arg Met Val Met Lys Leu Glu Ser Asp Lys Thr Phe 115 120 125 Pro Ile Met Leu Glu Gly Lys Ile Asn Gly Tyr Ala Cys Val Val Gly 130 135 140 Gly Lys Leu Phe Arg Pro Met His Val Glu Gly Lys Ile Asp Asn Asp 145 150 155 160 Val Leu Ala Ala Leu Lys Thr Lys Lys Ala Ser Lys Tyr Asp Leu Glu 165 170 175 Tyr Ala Asp Val Pro Gln Asn Met Arg Ala Asp Thr Phe Lys Tyr Thr 180 185 190 His Glu Lys Pro Gln Gly Tyr Tyr Ser Trp His His Gly Ala Val Gln 195 200 205 Tyr Glu Asn Gly Arg Phe Thr Val Pro Lys Gly Val Gly Ala Lys Gly 210 215 220 Asp Ser Gly Arg Pro Ile Leu Asp Asn Gln Gly Arg Val Val Ala Ile 225 230 235 240 Val Leu Gly Gly Val Asn Glu Gly Ser Arg Thr Ala Leu Ser Val Val 245 250 255 Met Trp Asn Glu Lys Gly Val Thr Val Lys Tyr Thr Pro Glu Asn Cys 260 265 270 Glu Gln Trp Ser Leu Val Thr Thr Met Cys Leu Leu Ala Asn Val Thr 275 280 285 Phe Pro Cys Ala Gln Pro Pro Ile Cys Tyr Asp Arg Lys Pro Ala Glu 290 295 300 Thr Leu Ala Met Leu Ser Val Asn Val Asp Asn Pro Gly Tyr Asp Glu 305 310 315 320 Leu Leu Glu Ala Ala Val Lys Cys Pro Gly Arg Lys Arg Arg Ser Thr 325 330 335 Glu Glu Leu Phe Asn Glu Tyr Lys Leu Thr Arg Pro Tyr Met Ala Arg 340 345 350 Cys Ile Arg Cys Ala Val Gly Ser Cys His Ser Pro Ile Ala Ile Glu 355 360 365 Ala Val Lys Ser Asp Gly His Asp Gly Tyr Val Arg Leu Gln Thr Ser 370 375 380 Ser Gln Tyr Gly Leu Asp Ser Ser Gly Asn Leu Lys Gly Arg Thr Met 385 390 395 400 Arg Tyr Asp Met His Gly Thr Ile Lys Glu Ile Pro Leu His Gln Val 405 410 415 Ser Leu Tyr Thr Ser Arg Pro Cys His Ile Val Asp Gly His Gly Tyr 420 425 430 Phe Leu Leu Ala Arg Cys Pro Ala Gly Asp Ser Ile Thr Met Glu Phe 435 440 445 Lys Lys Asp Ser Val Arg His Ser Cys Ser Val Pro Tyr Glu Val Lys 450 455 460 Phe Asn Pro Val Gly Arg Glu Leu Tyr Thr His Pro Pro Glu His Gly 465 470 475 480 Val Glu Gln Ala Cys Gln Val Tyr Ala His Asp Ala Gln Asn Arg Gly 485 490 495 Ala Tyr Val Glu Met His Leu Pro Gly Ser Glu Val Asp Ser Ser Leu 500 505 510 Val Ser Leu Ser Gly Ser Ser Gly Gly Asn Pro Asn Ala Asn Pro Asn 515 520 525 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 530 535 540 Val Asp Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 545 550 555 560 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 565 570 575 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 580 585 590 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 595 600 605 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Gly Gly Ser 610 615 620 Ser Val Thr Val Thr Pro Pro Asp Gly Thr Ser Ala Leu Val Glu Cys 625 630 635 640 Glu Cys Gly Gly Thr Lys Ile Ser Glu Thr Ile Asn Lys Thr Lys Gln 645 650 655 Phe Ser Gln Cys Thr Lys Lys Glu Gln Cys Arg Ala Tyr Arg Leu Gln 660 665 670 Asn Asp Lys Trp Val Tyr Asn Ser Asp Lys Leu Pro Lys Ala Ala Gly 675 680 685 Ala Thr Leu Lys Gly Lys Leu His Val Pro Phe Leu Leu Ala Asp Gly 690 695 700 Lys Cys Thr Val Pro Leu Ala Pro Glu Pro Met Ile Thr Phe Gly Phe 705 710 715 720 Arg Ser Val Ser Leu Lys Leu His Pro Lys Asn Pro Thr Tyr Leu Ile 725 730 735 Thr Arg Gln Leu Ala Asp Glu Pro His Tyr Thr His Glu Leu Ile Ser 740 745 750 Glu Pro Ala Val Arg Asn Phe Thr Val Thr Glu Lys Gly Trp Glu Phe 755 760 765 Val Trp Gly Asn His Pro Pro Lys Arg Phe Trp Ala Gln Glu Thr Ala 770 775 780 Pro Gly Asn Pro His Gly Leu Pro His Glu Val Ile Thr His Tyr Tyr 785 790 795 800 His Arg Tyr Pro Met Ser Thr Ile Leu Gly Leu Ser Ile Cys Ala Ala 805 810 815 Ile Ala Thr Val Ser Val Ala Ala Ser Thr Trp Leu Phe Cys Arg Ser 820 825 830 Arg Val Ala Cys Leu Thr Pro Tyr Arg Leu Thr Pro Asn Ala Arg Ile 835 840 845 Pro Phe Cys Leu Ala Val Leu Cys Cys Ala Arg Thr Ala Arg Ala Glu 850 855 860 Thr Thr Trp Glu Ser Leu Asp His Leu Trp Asn Asn Asn Gln Gln Met 865 870 875 880 Phe Trp Ile Gln Leu Leu Ile Pro Leu Ala Ala Leu Ile Val Val Thr 885 890 895 Arg Leu Leu Arg Cys Val Cys Cys Val Val Pro Phe Leu Val Met Ala 900 905 910 Gly Ala Ala Gly Ala Gly Ala Tyr Glu His Ala Thr Thr Met Pro Ser 915 920 925 Gln Ala Gly Ile Ser Tyr Asn Thr Ile Val Asn Arg Ala Gly Tyr Ala 930 935 940 Pro Leu Pro Ile Ser Ile Thr Pro Thr Lys Ile Lys Leu Ile Pro Thr 945 950 955 960 Val Asn Leu Glu Tyr Val Thr Cys His Tyr Lys Thr Gly Met Asp Ser 965 970 975 Pro Ala Ile Lys Cys Cys Gly Ser Gln Glu Cys Thr Pro Thr Tyr Arg 980 985 990 Pro Asp Glu Gln Cys Lys Val Phe Thr Gly Val Tyr Pro Phe Met Trp 995 1000 1005 Gly Gly Ala Tyr Cys Phe Cys Asp Thr Glu Asn Thr Gln Val Ser 1010 1015 1020 Lys Ala Tyr Val Met Lys Ser Asp Asp Cys Leu Ala Asp His Ala 1025 1030 1035 Glu Ala Tyr Lys Ala His Thr Ala Ser Val Gln Ala Phe Leu Asn 1040 1045 1050 Ile Thr Val Gly Glu His Ser Ile Val Thr Thr Val Tyr Val Asn 1055 1060 1065 Gly Glu Thr Pro Val Asn Phe Asn Gly Val Lys Ile Thr Ala Gly 1070 1075 1080 Pro Leu Ser Thr Ala Trp Thr Pro Phe Asp Arg Lys Ile Val Gln 1085 1090 1095 Tyr Ala Gly Glu Ile Tyr Asn Tyr Asp Phe Pro Glu Tyr Gly Ala 1100 1105 1110 Gly Gln Pro Gly Ala Phe Gly Asp Ile Gln Ser Arg Thr Val Ser 1115 1120 1125 Ser Ser Asp Leu Tyr Ala Asn Thr Asn Leu Val Leu Gln Arg Pro 1130 1135 1140 Lys Ala Gly Ala Ile His Val Pro Tyr Thr Gln Ala Pro Ser Gly 1145 1150 1155 Phe Glu Gln Trp Lys Lys Asp Lys Ala Pro Ser Leu Lys Phe Thr 1160 1165 1170 Ala Pro Phe Gly Cys Glu Ile Tyr Thr Asn Pro Ile Arg Ala Glu 1175 1180 1185 Asn Cys Ala Val Gly Ser Ile Pro Leu Ala Phe Asp Ile Pro Asp 1190 1195 1200 Ala Leu Phe Thr Arg Val Ser Glu Thr Pro Thr Leu Ser Ala Ala 1205 1210 1215 Glu Cys Thr Leu Asn Glu Cys Val Tyr Ser Ser Asp Phe Gly Gly 1220 1225 1230 Ile Ala Thr Val Lys Tyr Ser Ala Ser Lys Ser Gly Lys Cys Ala 1235 1240 1245 Val His Val Pro Ser Gly Thr Ala Thr Leu Lys Glu Ala Ala Val 1250 1255 1260 Glu Leu Thr Glu Gln Gly Ser Ala Thr Ile His Phe Ser Thr Ala 1265 1270 1275 Asn Ile His Pro Glu Phe Arg Leu Gln Ile Cys Thr Ser Tyr Val 1280 1285 1290 Thr Cys Lys Gly Asp Cys His Pro Pro Lys Asp His Ile Val Thr 1295 1300 1305 His Pro Gln Tyr His Ala Gln Thr Phe Thr Ala Ala Val Ser Lys 1310 1315 1320 Thr Ala Trp Thr Trp Leu Thr Ser Leu Leu Gly Gly Ser Ala Val 1325 1330 1335 Ile Ile Ile Ile Gly Leu Val Leu Ala Thr Ile Val Ala Met Tyr 1340 1345 1350 Val Leu Thr Asn Gln Lys His Asn 1355 1360 <210> 35 <211> 8509 <212> DNA <213> Artificial <220> <223> VLP74_21 (VEEV VLP 519 NPNAx6) whole sequence <400> 35 gaattcccat tgcatacgtt gtatccatat cataatatgt acatttatat tggctcatgt 60 ccaacattac cgccatgttg acattgatta ttgactagtt attaatagta atcaattacg 120 gggtcattag ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc 180 ccgcctggct gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc 240 atagtaacgc caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact 300 gcccacttgg cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat 360 gacggtaaat ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact 420 tggcagtaca tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac 480 atcaatgggc gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac 540 gtcaatggga gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac 600 tccgccccat tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga 660 gctcgtttag tgaaccgtca gatcgcctgg agacgccatc cacgctgttt tgacctccat 720 agaagacacc gggaccgatc cagcctccgt taacggtgga gggcagtgta gtctgagcag 780 tactcgttgc tgccgcgcgc gccaccagac ataatagctg acagactaac agactgttcc 840 tttccatggg tcttttctgc agtcaccgtc gtcgacacgt gtgatcagat atcgcggccg 900 ccaccatgtt cccgttccag ccaatgtatc cgatgcagcc aatgccctat cgcaacccgt 960 tcgcggcccc gcgcaggccc tggttcccca gaaccgaccc ttttctggcg atgcaggtgc 1020 aggaattaac ccgctcgatg gctaacctga cgttcaagca acgccgggac gcgccacctg 1080 aggggccatc cgctaataaa ccgaagaagg aggcctcgca aaaacagaaa gggggaggcc 1140 aagggaagaa gaagaagaac caagggaaga agaaggctaa gacagggccg cctaatccga 1200 aggcacagaa tggaaacaag aagaagacca acaagaaacc aggcaagaga cagcgcatgg 1260 tcatgaaatt ggaatctgac aagacgttcc caatcatgtt ggaagggaag ataaacggct 1320 acgcttgtgt ggtcggaggg aagttattca ggccgatgca tgtggaaggc aagatcgaca 1380 acgacgttct ggccgcgctt aagacgaaga aagcatccaa atacgatctt gagtatgcag 1440 atgtgccaca gaacatgcgg gccgatacat tcaaatacac ccatgagaaa ccccaaggct 1500 attacagctg gcatcatgga gcagtccaat atgaaaatgg gcgtttcacg gtgccgaaag 1560 gagttggggc caagggagac agcggacgac ccattctgga taaccaggga cgggtggtcg 1620 ctattgtgct gggaggtgtg aatgaaggat ctaggacagc cctttcagtc gtcatgtgga 1680 acgagaaggg agttaccgtg aagtatactc cagagaactg cgagcaatgg tcactagtga 1740 ccaccatgtg tctgctcgcc aatgtgacgt tcccatgtgc tcaaccacca atttgctacg 1800 acagaaaacc agcagagact ttggccatgc tcagcgttaa cgttgacaac ccgggctacg 1860 atgagctgct ggaagcagct gttaagtgcc ccggaaggaa aaggagatcc accgaggagc 1920 tgtttaatga gtataagcta acgcgccctt acatggccag atgcatcaga tgtgcagttg 1980 ggagctgcca tagtccaata gcaatcgagg cagtaaagag cgacgggcac gacggttatg 2040 ttagacttca gacttcctcg cagtatggcc tggattcctc cggcaactta aagggcagga 2100 ccatgcggta tgacatgcac gggaccatta aagagatacc actacatcaa gtgtcactct 2160 atacatctcg cccgtgtcac attgtggatg ggcacggtta tttcctgctt gccaggtgcc 2220 cggcagggga ctccatcacc atggaattta agaaagattc cgtcagacac tcctgctcgg 2280 tgccgtatga agtgaaattt aatcctgtag gcagagaact ctatactcat cccccagaac 2340 acggagtaga gcaagcgtgc caagtctacg cacatgatgc acagaacaga ggagcttatg 2400 tcgagatgca cctcccgggc tcagaagtgg acagcagttt ggtttccttg agcggcagtt 2460 ccggaggaaa cccgaatgcc aatcccaacg cgaaccccaa tgctaaccca aatgccaacc 2520 caaacgccaa ccccaacgct ggtggatcct cagtcaccgt gacacctcct gatgggacta 2580 gcgccctggt ggaatgcgag tgtggcggca caaagatctc cgagaccatc aacaagacaa 2640 aacagttcag ccagtgcaca aagaaggagc agtgcagagc atatcggctg cagaacgata 2700 agtgggtgta taattctgac aaactgccca aagcagcggg agccacctta aaaggaaaac 2760 tgcatgtccc attcttgctg gcagacggca aatgcaccgt gcctctagca ccagaaccta 2820 tgataacctt cggtttcaga tcagtgtcac tgaaactgca ccctaagaat cccacatatc 2880 taatcacccg ccaacttgct gatgagcctc actacacgca cgagctcata tctgaaccag 2940 ctgttaggaa ttttaccgtc accgaaaaag ggtgggagtt tgtatgggga aaccacccgc 3000 cgaaaaggtt ttgggcacag gaaacagcac ccggaaatcc acatgggcta ccgcacgagg 3060 tgataactca ttattaccac agatacccta tgtccaccat cctgggtttg tcaatttgtg 3120 ccgccattgc aaccgtttcc gttgcagcgt ctacctggct gttttgcaga tcaagagttg 3180 cgtgcctaac tccttaccgg ctaacaccta acgctaggat accattttgt ctggctgtgc 3240 tttgctgcgc ccgcactgcc cgggccgaga ccacctggga gtccttggat cacctatgga 3300 acaataacca acagatgttc tggattcaat tgctgatccc tctggccgcc ttgatcgtag 3360 tgactcgcct gctcaggtgc gtgtgctgtg tcgtgccttt tttagtcatg gccggcgccg 3420 caggcgccgg cgcctacgag cacgcgacca cgatgccgag ccaagcggga atctcgtata 3480 acactatagt caacagagca ggctacgcac cactccctat cagcataaca ccaacaaaga 3540 tcaagctgat acctacagtg aacttggagt acgtcacctg ccactacaaa acaggaatgg 3600 attcaccagc catcaaatgc tgcggatctc aggaatgcac tccaacttac aggcctgatg 3660 aacagtgcaa agtcttcaca ggggtttacc cgttcatgtg gggtggtgca tattgctttt 3720 gcgacactga gaacacccaa gtcagcaagg cctacgtaat gaaatctgac gactgccttg 3780 cggatcatgc tgaagcatat aaagcgcaca cagcctcagt gcaggcgttc ctcaacatca 3840 cagtgggaga acactctatt gtgactaccg tgtatgtgaa tggagaaact cctgtgaatt 3900 tcaatggggt caaaataact gcaggtccgc tttccacagc ttggacaccc tttgatcgca 3960 aaatcgtgca gtatgccggg gagatctata attatgattt tcctgagtat ggggcaggac 4020 aaccaggagc atttggagat atacaatcca gaacagtctc aagctctgat ctgtatgcca 4080 ataccaacct agtgctgcag agacccaaag caggagcgat ccacgtgcca tacactcagg 4140 caccttcggg ttttgagcaa tggaagaaag ataaagctcc atcattgaaa tttaccgccc 4200 ctttcggatg cgaaatatat acaaacccca ttcgcgccga aaactgtgct gtagggtcaa 4260 ttccattagc ctttgacatt cccgacgcct tgttcaccag ggtgtcagaa acaccgacac 4320 tttcagcggc cgaatgcact cttaacgagt gcgtgtattc ttccgacttt ggtgggatcg 4380 ccacggtcaa gtactcggcc agcaagtcag gcaagtgcgc agtccatgtg ccatcaggga 4440 ctgctaccct aaaagaagca gcagtcgagc taaccgagca agggtcggcg actatccatt 4500 tctcgaccgc aaatatccac ccggagttca ggctccaaat atgcacatca tatgttacgt 4560 gcaaaggtga ttgtcacccc ccgaaagacc atattgtgac acaccctcag tatcacgccc 4620 aaacatttac agccgcggtg tcaaaaaccg cgtggacgtg gttaacatcc ctgctgggag 4680 gatcagccgt aattattata attggcttgg tgctggctac tattgtggcc atgtacgtgc 4740 tgaccaacca gaaacataat taaggatcta gatctgctgt gccttctagt tgccagccat 4800 ctgttgtttg cccctccccc gtgccttcct tgaccctgga aggtgccact cccactgtcc 4860 tttcctaata aaatgaggaa attgcatcgc attgtctgag taggtgtcat tctattctgg 4920 ggggtggggt ggggcaggac agcaaggggg aggattggga agacaatagc aggcatgctg 4980 gggatgcggt gggctctatg ggtacccagg tgctgaagaa ttgacccggt tcctcctggg 5040 ccagaaagaa gcaggcacat ccccttctct gtgacacacc ctgtccacgc ccctggttct 5100 tagttccagc cccactcata ggacactcat agctcaggag ggctccgcct tcaatcccac 5160 ccgctaaagt acttggagcg gtctctccct ccctcatcag cccaccaaac caaacctagc 5220 ctccaagagt gggaagaaat taaagcaaga taggctatta agtgcagagg gagagaaaat 5280 gcctccaaca tgtgaggaag taatgagaga aatcatagaa ttttaaggcc atgatttaag 5340 gccatcatgg cctaagcttg aaaggagata ggatcaaagc ttggcgtaat catggtcata 5400 gctgtttcct gtgtgaaatt gttatccgct cacaattcca cacaacatac gagccggaag 5460 cataaagtgt aaagcctggg gtgcctaatg agtgagctaa ctcacattaa ttgcgttgcg 5520 ctcactgccc gctttccagt cgggaaacct gtcgtgccag ctgcattaat gaatcggcca 5580 acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc gcttcctcgc tcactgactc 5640 gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct cactcaaagg cggtaatacg 5700 gttatccaca gaatcagggg ataacgcagg aaagaacatg tgagcaaaag gccagcaaaa 5760 ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc cataggctcc gcccccctga 5820 cgagcatcac aaaaatcgac gctcaagtca gaggtggcga aacccgacag gactataaag 5880 ataccaggcg tttccccctg gaagctccct cgtgcgctct cctgttccga ccctgccgct 5940 taccggatac ctgtccgcct ttctcccttc gggaagcgtg gcgctttctc atagctcacg 6000 ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag ctgggctgtg tgcacgaacc 6060 ccccgttcag cccgaccgct gcgccttatc cggtaactat cgtcttgagt ccaacccggt 6120 aagacacgac ttatcgccac tggcagcagc cactggtaac aggattagca gagcgaggta 6180 tgtaggcggt gctacagagt tcttgaagtg gtggcctaac tacggctaca ctagaagaac 6240 agtatttggt atctgcgctc tgctgaagcc agttaccttc ggaaaaagag ttggtagctc 6300 ttgatccggc aaacaaacca ccgctggtag cggtggtttt tttgtttgca agcagcagat 6360 tacgcgcaga aaaaaaggat ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc 6420 tcagtggaac gaaaactcac gttaagggat tttggtcatg agattatcaa aaaggatctt 6480 cacctagatc cttttaaatt aaaaatgaag ttttaaatca atctaaagta tatatgagta 6540 aacttggtct gacagttacc aatgcttaat cagtgaggca cctatctcag cgatctgtct 6600 atttcgttca tccatagttg cctgactccc cgtcgtgtag ataactacga tacgggaggg 6660 cttaccatct ggccccagtg ctgcaatgat accgcgagaa ccacgctcac cggctccaga 6720 tttatcagca ataaaccagc cagccggaag ggccgagcgc agaagtggtc ctgcaacttt 6780 atccgcctcc atccagtcta ttaattgttg ccgggaagct agagtaagta gttcgccagt 6840 taatagtttg cgcaacgttg ttgccattgc tacaggcatc gtggtgtcac gctcgtcgtt 6900 tggtatggct tcattcagct ccggttccca acgatcaagg cgagttacat gatcccccat 6960 gttgtgcaaa aaagcggtta gctccttcgg tcctccgatc gttgtcagaa gtaagttggc 7020 cgcagtgtta tcactcatgg ttatggcagc actgcataat tctcttactg tcatgccatc 7080 cgtaagatgc ttttctgtga ctggtgagta ctcaaccaag tcattctgag aatagtgtat 7140 gcggcgaccg agttgctctt gcccggcgtc aatacgggat aataccgcgc cacatagcag 7200 aactttaaaa gtgctcatca ttggaaaacg ttcttcgggg cgaaaactct caaggatctt 7260 accgctgttg agatccagtt cgatgtaacc cactcgtgca cccaactgat cttcagcatc 7320 ttttactttc accagcgttt ctgggtgagc aaaaacagga aggcaaaatg ccgcaaaaaa 7380 gggaataagg gcgacacgga aatgttgaat actcatactc ttcctttttc aatattattg 7440 aagcatttat cagggttatt gtctcatgag cggatacata tttgaatgta tttagaaaaa 7500 taaacaaata ggggttccgc gcacatttcc ccgaaaagtg ccacctgacg tctaagaaac 7560 cattattatc atgacattaa cctataaaaa taggcgtatc acgaggccct ttcgggtcgc 7620 gcgtttcggt gatgacggtg aaaacctctg acacatgcag ctcccgttga cggtcacagc 7680 ttgtctgtaa gcggatgccg ggagcagaca agcccgtcag ggcgcgtcag cgggtgttgg 7740 cgggtgtcgg ggctggctta actatgcggc atcagagcag attgtactga gagtgcacca 7800 taaaattgta aacgttaata ttttgttaaa attcgcgtta aatttttgtt aaatcagctc 7860 attttttaac caataggccg aaatcggcaa aatcccttat aaatcaaaag aatagcccga 7920 gatagggttg agtgttgttc cagtttggaa caagagtcca ctattaaaga acgtggactc 7980 caacgtcaaa gggcgaaaaa ccgtctatca gggcgatggc ccactacgtg aaccatcacc 8040 caaatcaagt tttttggggt cgaggtgccg taaagcacta aatcggaacc ctaaagggag 8100 cccccgattt agagcttgac ggggaaagcc ggcgaacgtg gcgagaaagg aagggaagaa 8160 agcgaaagga gcgggcgcta gggcgctggc aagtgtagcg gtcacgctgc gcgtaaccac 8220 cacacccgcc gcgcttaatg cgccgctaca gggcgcgtac tatggttgct ttgacgtatg 8280 cggtgtgaaa taccgcacag atgcgtaagg agaaaatacc gcatcaggcg ccattcgcca 8340 ttcaggctgc gcaactgttg ggaagggcga tcggtgcggg cctcttcgct attacgccag 8400 ctggcgaaag ggggatgtgc tgcaaggcga ttaagttggg taacgccagg gttttcccag 8460 tcacgacgtt gtaaaacgac ggccagtgaa ttccatggtc tcaactttc 8509 <210> 36 <211> 3858 <212> DNA <213> Artificial <220> <223> VLP74_21 (VEEV VLP 519 NPNAx6) VEEV-NPNAx6 sequence only <400> 36 atgttcccgt tccagccaat gtatccgatg cagccaatgc cctatcgcaa cccgttcgcg 60 gccccgcgca ggccctggtt ccccagaacc gacccttttc tggcgatgca ggtgcaggaa 120 ttaacccgct cgatggctaa cctgacgttc aagcaacgcc gggacgcgcc acctgagggg 180 ccatccgcta ataaaccgaa gaaggaggcc tcgcaaaaac agaaaggggg aggccaaggg 240 aagaagaaga agaaccaagg gaagaagaag gctaagacag ggccgcctaa tccgaaggca 300 cagaatggaa acaagaagaa gaccaacaag aaaccaggca agagacagcg catggtcatg 360 aaattggaat ctgacaagac gttcccaatc atgttggaag ggaagataaa cggctacgct 420 tgtgtggtcg gagggaagtt attcaggccg atgcatgtgg aaggcaagat cgacaacgac 480 gttctggccg cgcttaagac gaagaaagca tccaaatacg atcttgagta tgcagatgtg 540 ccacagaaca tgcgggccga tacattcaaa tacacccatg agaaacccca aggctattac 600 agctggcatc atggagcagt ccaatatgaa aatgggcgtt tcacggtgcc gaaaggagtt 660 ggggccaagg gagacagcgg acgacccatt ctggataacc agggacgggt ggtcgctatt 720 gtgctgggag gtgtgaatga aggatctagg acagcccttt cagtcgtcat gtggaacgag 780 aagggagtta ccgtgaagta tactccagag aactgcgagc aatggtcact agtgaccacc 840 atgtgtctgc tcgccaatgt gacgttccca tgtgctcaac caccaatttg ctacgacaga 900 aaaccagcag agactttggc catgctcagc gttaacgttg acaacccggg ctacgatgag 960 ctgctggaag cagctgttaa gtgccccgga aggaaaagga gatccaccga ggagctgttt 1020 aatgagtata agctaacgcg cccttacatg gccagatgca tcagatgtgc agttgggagc 1080 tgccatagtc caatagcaat cgaggcagta aagagcgacg ggcacgacgg ttatgttaga 1140 cttcagactt cctcgcagta tggcctggat tcctccggca acttaaaggg caggaccatg 1200 cggtatgaca tgcacgggac cattaaagag ataccactac atcaagtgtc actctataca 1260 tctcgcccgt gtcacattgt ggatgggcac ggttatttcc tgcttgccag gtgcccggca 1320 ggggactcca tcaccatgga atttaagaaa gattccgtca gacactcctg ctcggtgccg 1380 tatgaagtga aatttaatcc tgtaggcaga gaactctata ctcatccccc agaacacgga 1440 gtagagcaag cgtgccaagt ctacgcacat gatgcacaga acagaggagc ttatgtcgag 1500 atgcacctcc cgggctcaga agtggacagc agtttggttt ccttgagcgg cagttccgga 1560 ggaaacccga atgccaatcc caacgcgaac cccaatgcta acccaaatgc caacccaaac 1620 gccaacccca acgctggtgg atcctcagtc accgtgacac ctcctgatgg gactagcgcc 1680 ctggtggaat gcgagtgtgg cggcacaaag atctccgaga ccatcaacaa gacaaaacag 1740 ttcagccagt gcacaaagaa ggagcagtgc agagcatatc ggctgcagaa cgataagtgg 1800 gtgtataatt ctgacaaact gcccaaagca gcgggagcca ccttaaaagg aaaactgcat 1860 gtcccattct tgctggcaga cggcaaatgc accgtgcctc tagcaccaga acctatgata 1920 accttcggtt tcagatcagt gtcactgaaa ctgcacccta agaatcccac atatctaatc 1980 acccgccaac ttgctgatga gcctcactac acgcacgagc tcatatctga accagctgtt 2040 aggaatttta ccgtcaccga aaaagggtgg gagtttgtat ggggaaacca cccgccgaaa 2100 aggttttggg cacaggaaac agcacccgga aatccacatg ggctaccgca cgaggtgata 2160 actcattatt accacagata ccctatgtcc accatcctgg gtttgtcaat ttgtgccgcc 2220 attgcaaccg tttccgttgc agcgtctacc tggctgtttt gcagatcaag agttgcgtgc 2280 ctaactcctt accggctaac acctaacgct aggataccat tttgtctggc tgtgctttgc 2340 tgcgcccgca ctgcccgggc cgagaccacc tgggagtcct tggatcacct atggaacaat 2400 aaccaacaga tgttctggat tcaattgctg atccctctgg ccgccttgat cgtagtgact 2460 cgcctgctca ggtgcgtgtg ctgtgtcgtg ccttttttag tcatggccgg cgccgcaggc 2520 gccggcgcct acgagcacgc gaccacgatg ccgagccaag cgggaatctc gtataacact 2580 atagtcaaca gagcaggcta cgcaccactc cctatcagca taacaccaac aaagatcaag 2640 ctgataccta cagtgaactt ggagtacgtc acctgccact acaaaacagg aatggattca 2700 ccagccatca aatgctgcgg atctcaggaa tgcactccaa cttacaggcc tgatgaacag 2760 tgcaaagtct tcacaggggt ttacccgttc atgtggggtg gtgcatattg cttttgcgac 2820 actgagaaca cccaagtcag caaggcctac gtaatgaaat ctgacgactg ccttgcggat 2880 catgctgaag catataaagc gcacacagcc tcagtgcagg cgttcctcaa catcacagtg 2940 ggagaacact ctattgtgac taccgtgtat gtgaatggag aaactcctgt gaatttcaat 3000 ggggtcaaaa taactgcagg tccgctttcc acagcttgga caccctttga tcgcaaaatc 3060 gtgcagtatg ccggggagat ctataattat gattttcctg agtatggggc aggacaacca 3120 ggagcatttg gagatataca atccagaaca gtctcaagct ctgatctgta tgccaatacc 3180 aacctagtgc tgcagagacc caaagcagga gcgatccacg tgccatacac tcaggcacct 3240 tcgggttttg agcaatggaa gaaagataaa gctccatcat tgaaatttac cgcccctttc 3300 ggatgcgaaa tatatacaaa ccccattcgc gccgaaaact gtgctgtagg gtcaattcca 3360 ttagcctttg acattcccga cgccttgttc accagggtgt cagaaacacc gacactttca 3420 gcggccgaat gcactcttaa cgagtgcgtg tattcttccg actttggtgg gatcgccacg 3480 gtcaagtact cggccagcaa gtcaggcaag tgcgcagtcc atgtgccatc agggactgct 3540 accctaaaag aagcagcagt cgagctaacc gagcaagggt cggcgactat ccatttctcg 3600 accgcaaata tccacccgga gttcaggctc caaatatgca catcatatgt tacgtgcaaa 3660 ggtgattgtc accccccgaa agaccatatt gtgacacacc ctcagtatca cgcccaaaca 3720 tttacagccg cggtgtcaaa aaccgcgtgg acgtggttaa catccctgct gggaggatca 3780 gccgtaatta ttataattgg cttggtgctg gctactattg tggccatgta cgtgctgacc 3840 aaccagaaac ataattaa 3858 <210> 37 <211> 1285 <212> PRT <213> Artificial <220> <223> VLP74_21 (VEEV VLP 519 NPNAx6) amino acid sequence <400> 37 Met Phe Pro Phe Gln Pro Met Tyr Pro Met Gln Pro Met Pro Tyr Arg 1 5 10 15 Asn Pro Phe Ala Ala Pro Arg Arg Pro Trp Phe Pro Arg Thr Asp Pro 20 25 30 Phe Leu Ala Met Gln Val Gln Glu Leu Thr Arg Ser Met Ala Asn Leu 35 40 45 Thr Phe Lys Gln Arg Arg Asp Ala Pro Pro Glu Gly Pro Ser Ala Asn 50 55 60 Lys Pro Lys Lys Glu Ala Ser Gln Lys Gln Lys Gly Gly Gly Gln Gly 65 70 75 80 Lys Lys Lys Lys Asn Gln Gly Lys Lys Lys Ala Lys Thr Gly Pro Pro 85 90 95 Asn Pro Lys Ala Gln Asn Gly Asn Lys Lys Lys Thr Asn Lys Lys Pro 100 105 110 Gly Lys Arg Gln Arg Met Val Met Lys Leu Glu Ser Asp Lys Thr Phe 115 120 125 Pro Ile Met Leu Glu Gly Lys Ile Asn Gly Tyr Ala Cys Val Val Gly 130 135 140 Gly Lys Leu Phe Arg Pro Met His Val Glu Gly Lys Ile Asp Asn Asp 145 150 155 160 Val Leu Ala Ala Leu Lys Thr Lys Lys Ala Ser Lys Tyr Asp Leu Glu 165 170 175 Tyr Ala Asp Val Pro Gln Asn Met Arg Ala Asp Thr Phe Lys Tyr Thr 180 185 190 His Glu Lys Pro Gln Gly Tyr Tyr Ser Trp His His Gly Ala Val Gln 195 200 205 Tyr Glu Asn Gly Arg Phe Thr Val Pro Lys Gly Val Gly Ala Lys Gly 210 215 220 Asp Ser Gly Arg Pro Ile Leu Asp Asn Gln Gly Arg Val Val Ala Ile 225 230 235 240 Val Leu Gly Gly Val Asn Glu Gly Ser Arg Thr Ala Leu Ser Val Val 245 250 255 Met Trp Asn Glu Lys Gly Val Thr Val Lys Tyr Thr Pro Glu Asn Cys 260 265 270 Glu Gln Trp Ser Leu Val Thr Thr Met Cys Leu Leu Ala Asn Val Thr 275 280 285 Phe Pro Cys Ala Gln Pro Pro Ile Cys Tyr Asp Arg Lys Pro Ala Glu 290 295 300 Thr Leu Ala Met Leu Ser Val Asn Val Asp Asn Pro Gly Tyr Asp Glu 305 310 315 320 Leu Leu Glu Ala Ala Val Lys Cys Pro Gly Arg Lys Arg Arg Ser Thr 325 330 335 Glu Glu Leu Phe Asn Glu Tyr Lys Leu Thr Arg Pro Tyr Met Ala Arg 340 345 350 Cys Ile Arg Cys Ala Val Gly Ser Cys His Ser Pro Ile Ala Ile Glu 355 360 365 Ala Val Lys Ser Asp Gly His Asp Gly Tyr Val Arg Leu Gln Thr Ser 370 375 380 Ser Gln Tyr Gly Leu Asp Ser Ser Gly Asn Leu Lys Gly Arg Thr Met 385 390 395 400 Arg Tyr Asp Met His Gly Thr Ile Lys Glu Ile Pro Leu His Gln Val 405 410 415 Ser Leu Tyr Thr Ser Arg Pro Cys His Ile Val Asp Gly His Gly Tyr 420 425 430 Phe Leu Leu Ala Arg Cys Pro Ala Gly Asp Ser Ile Thr Met Glu Phe 435 440 445 Lys Lys Asp Ser Val Arg His Ser Cys Ser Val Pro Tyr Glu Val Lys 450 455 460 Phe Asn Pro Val Gly Arg Glu Leu Tyr Thr His Pro Pro Glu His Gly 465 470 475 480 Val Glu Gln Ala Cys Gln Val Tyr Ala His Asp Ala Gln Asn Arg Gly 485 490 495 Ala Tyr Val Glu Met His Leu Pro Gly Ser Glu Val Asp Ser Ser Leu 500 505 510 Val Ser Leu Ser Gly Ser Ser Gly Gly Asn Pro Asn Ala Asn Pro Asn 515 520 525 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 530 535 540 Ala Gly Gly Ser Ser Val Thr Val Thr Pro Pro Asp Gly Thr Ser Ala 545 550 555 560 Leu Val Glu Cys Glu Cys Gly Gly Thr Lys Ile Ser Glu Thr Ile Asn 565 570 575 Lys Thr Lys Gln Phe Ser Gln Cys Thr Lys Lys Glu Gln Cys Arg Ala 580 585 590 Tyr Arg Leu Gln Asn Asp Lys Trp Val Tyr Asn Ser Asp Lys Leu Pro 595 600 605 Lys Ala Ala Gly Ala Thr Leu Lys Gly Lys Leu His Val Pro Phe Leu 610 615 620 Leu Ala Asp Gly Lys Cys Thr Val Pro Leu Ala Pro Glu Pro Met Ile 625 630 635 640 Thr Phe Gly Phe Arg Ser Val Ser Leu Lys Leu His Pro Lys Asn Pro 645 650 655 Thr Tyr Leu Ile Thr Arg Gln Leu Ala Asp Glu Pro His Tyr Thr His 660 665 670 Glu Leu Ile Ser Glu Pro Ala Val Arg Asn Phe Thr Val Thr Glu Lys 675 680 685 Gly Trp Glu Phe Val Trp Gly Asn His Pro Pro Lys Arg Phe Trp Ala 690 695 700 Gln Glu Thr Ala Pro Gly Asn Pro His Gly Leu Pro His Glu Val Ile 705 710 715 720 Thr His Tyr Tyr His Arg Tyr Pro Met Ser Thr Ile Leu Gly Leu Ser 725 730 735 Ile Cys Ala Ala Ile Ala Thr Val Ser Val Ala Ala Ser Thr Trp Leu 740 745 750 Phe Cys Arg Ser Arg Val Ala Cys Leu Thr Pro Tyr Arg Leu Thr Pro 755 760 765 Asn Ala Arg Ile Pro Phe Cys Leu Ala Val Leu Cys Cys Ala Arg Thr 770 775 780 Ala Arg Ala Glu Thr Thr Trp Glu Ser Leu Asp His Leu Trp Asn Asn 785 790 795 800 Asn Gln Gln Met Phe Trp Ile Gln Leu Leu Ile Pro Leu Ala Ala Leu 805 810 815 Ile Val Val Thr Arg Leu Leu Arg Cys Val Cys Cys Val Val Pro Phe 820 825 830 Leu Val Met Ala Gly Ala Ala Gly Ala Gly Ala Tyr Glu His Ala Thr 835 840 845 Thr Met Pro Ser Gln Ala Gly Ile Ser Tyr Asn Thr Ile Val Asn Arg 850 855 860 Ala Gly Tyr Ala Pro Leu Pro Ile Ser Ile Thr Pro Thr Lys Ile Lys 865 870 875 880 Leu Ile Pro Thr Val Asn Leu Glu Tyr Val Thr Cys His Tyr Lys Thr 885 890 895 Gly Met Asp Ser Pro Ala Ile Lys Cys Cys Gly Ser Gln Glu Cys Thr 900 905 910 Pro Thr Tyr Arg Pro Asp Glu Gln Cys Lys Val Phe Thr Gly Val Tyr 915 920 925 Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Thr Glu Asn Thr 930 935 940 Gln Val Ser Lys Ala Tyr Val Met Lys Ser Asp Asp Cys Leu Ala Asp 945 950 955 960 His Ala Glu Ala Tyr Lys Ala His Thr Ala Ser Val Gln Ala Phe Leu 965 970 975 Asn Ile Thr Val Gly Glu His Ser Ile Val Thr Thr Val Tyr Val Asn 980 985 990 Gly Glu Thr Pro Val Asn Phe Asn Gly Val Lys Ile Thr Ala Gly Pro 995 1000 1005 Leu Ser Thr Ala Trp Thr Pro Phe Asp Arg Lys Ile Val Gln Tyr 1010 1015 1020 Ala Gly Glu Ile Tyr Asn Tyr Asp Phe Pro Glu Tyr Gly Ala Gly 1025 1030 1035 Gln Pro Gly Ala Phe Gly Asp Ile Gln Ser Arg Thr Val Ser Ser 1040 1045 1050 Ser Asp Leu Tyr Ala Asn Thr Asn Leu Val Leu Gln Arg Pro Lys 1055 1060 1065 Ala Gly Ala Ile His Val Pro Tyr Thr Gln Ala Pro Ser Gly Phe 1070 1075 1080 Glu Gln Trp Lys Lys Asp Lys Ala Pro Ser Leu Lys Phe Thr Ala 1085 1090 1095 Pro Phe Gly Cys Glu Ile Tyr Thr Asn Pro Ile Arg Ala Glu Asn 1100 1105 1110 Cys Ala Val Gly Ser Ile Pro Leu Ala Phe Asp Ile Pro Asp Ala 1115 1120 1125 Leu Phe Thr Arg Val Ser Glu Thr Pro Thr Leu Ser Ala Ala Glu 1130 1135 1140 Cys Thr Leu Asn Glu Cys Val Tyr Ser Ser Asp Phe Gly Gly Ile 1145 1150 1155 Ala Thr Val Lys Tyr Ser Ala Ser Lys Ser Gly Lys Cys Ala Val 1160 1165 1170 His Val Pro Ser Gly Thr Ala Thr Leu Lys Glu Ala Ala Val Glu 1175 1180 1185 Leu Thr Glu Gln Gly Ser Ala Thr Ile His Phe Ser Thr Ala Asn 1190 1195 1200 Ile His Pro Glu Phe Arg Leu Gln Ile Cys Thr Ser Tyr Val Thr 1205 1210 1215 Cys Lys Gly Asp Cys His Pro Pro Lys Asp His Ile Val Thr His 1220 1225 1230 Pro Gln Tyr His Ala Gln Thr Phe Thr Ala Ala Val Ser Lys Thr 1235 1240 1245 Ala Trp Thr Trp Leu Thr Ser Leu Leu Gly Gly Ser Ala Val Ile 1250 1255 1260 Ile Ile Ile Gly Leu Val Leu Ala Thr Ile Val Ala Met Tyr Val 1265 1270 1275 Leu Thr Asn Gln Lys His Asn 1280 1285 <210> 38 <211> 7305 <212> DNA <213> Artificial <220> <223> VLP74_15 (CHI VLP 532 NPNAx6) Whole sequence <400> 38 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240 attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300 tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360 tttcccagtc acgacgttgt aaaacgacgg ccagtgaatt gacgcgtgtt ggcattgatt 420 attgactagt tattaatagt aatcaattac ggggtcatta gttcatagcc catatatgga 480 gttccgcgtt acataactta cggtaaatgg cccgcctggc tgaccgccca acgacccccg 540 cccattgacg tcaataatga cgtatgttcc catagtaacg ccaataggga ctttccattg 600 acgtcaatgg gtggagtatt tacggtaaac tgcccacttg gcagtacatc aagtgtatca 660 tatgccaagt acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct ggcattatgc 720 ccagtacatg accttatggg actttcctac ttggcagtac atctacgtat tagtcatcgc 780 tattaccatg gtgatgcggt tttggcagta catcaatggg cgtggatagc ggtttgactc 840 acggggattt ccaagtctcc accccattga cgtcaatggg agtttgtttt ggcaccaaaa 900 tcaacgggac tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa tgggcggtag 960 gcgtgtacgg tgggaggtct atataagcag agctcgttta gtgaaccgtc agataactgc 1020 aggtcgacga tatcgcggcc gccaccatgg agttcatccc gacgcaaact ttctataaca 1080 gaaggtacca accccgaccc tgggccccac gccctacaat tcaagtaatt agacctagac 1140 cacgtccaca gaggcaggct gggcaactcg cccagctgat ctccgcagtc aacaaattga 1200 ccatgcgcgc ggtacctcaa cagaagcctc gcagaaatcg gaaaaacaag aagcaaaggc 1260 agaagaagca ggcgccgcaa aacgacccaa agcaaaagaa gcaaccacca caaaagaagc 1320 cggctcaaaa gaagaagaaa ccaggccgta gggagagaat gtgcatgaaa attgaaaatg 1380 attgcatctt cgaagtcaag catgaaggca aagtgatggg ctacgcatgc ctggtggggg 1440 ataaagtaat gaaaccagca catgtgaagg gaactatcga caatgccgat ctggctaaac 1500 tggcctttaa gcggtcgtct aaatacgatc ttgaatgtgc acagataccg gtgcacatga 1560 agtctgatgc ctcgaagttt acccacgaga aacccgaggg gtactataac tggcatcacg 1620 gagcagtgca gtattcagga ggccggttca ctatcccgac gggtgcaggc aagccgggag 1680 acagcggcag accgatcttc gacaacaaag gacgggtggt ggccatcgtc ctaggagggg 1740 ccaacgaagg tgcccgcacg gccctctccg tggtgacgtg gaacaaagac atcgtcacaa 1800 aaattacccc tgagggagcc gaagagtgga gcctcgccct cccggtcttg tgcctgttgg 1860 caaacactac attcccctgc tctcagccgc cttgcacacc ctgctgctac gaaaaggaac 1920 cggaaagcac cttgcgcatg cttgaggaca acgtgatgag acccggatac taccagctac 1980 taaaagcatc gctgacttgc tctccccacc gccaaagacg cagtactaag gacaatttta 2040 atgtctataa agccacaaga ccatatctag ctcattgtcc tgactgcgga gaagggcatt 2100 cgtgccacag ccctatcgca ttggagcgca tcagaaatga agcaacggac ggaacgctga 2160 aaatccaggt ctctttgcag atcgggataa agacagatga cagccacgat tggaccaagc 2220 tgcgctatat ggatagccat acgccagcgg acgcggagcg agccggattg cttgtaagga 2280 cttcagcacc gtgcacgatc accgggacca tgggacactt tattctcgcc cgatgcccga 2340 aaggagagac gctgacagtg ggatttacgg acagcagaaa gatcagccac acatgcacac 2400 acccgttcca tcatgaacca cctgtgatag gtagggagag gttccactct cgaccacaac 2460 atggtaaaga gttaccttgc agcacgtacg tgcagagcac cgctgccact gctgaggaga 2520 tagaggtgca tatgccccca gatactcctg accgcacgct gatgacgcag cagtctggca 2580 acgtgaagat cacagttaat gggcagacgg tgcggtacaa gtgcaactgc ggtggctccg 2640 gaggaaaccc gaatgccaat cccaacgcga accccaatgc taacccaaat gccaacccaa 2700 acgccaaccc caacgctggt ggatccaacg agggactgac aaccacagac aaagtgatca 2760 ataactgcaa aattgatcag tgccatgctg cagtcactaa tcacaagaat tggcaataca 2820 actccccttt agtcccgcgc aacgctgaac tcggggaccg taaaggaaag atccacatcc 2880 cattcccatt ggcaaacgtg acttgcagag tgccaaaagc aagaaaccct acagtaactt 2940 acggaaaaaa ccaagtcacc atgctgctgt atcctgacca tccgacactc ttgtcttacc 3000 gtaacatggg acaggaacca aattaccacg aggagtgggt gacacacaag aaggaggtta 3060 ccttgaccgt gcctactgag ggtctggagg tcacttgggg caacaacgaa ccatacaagt 3120 actggccgca gatgtctacg aacggtactg ctcatggtca cccacatgag ataatcttgt 3180 actattatga gctgtacccc actatgactg tagtcattgt gtcggtggcc tcgttcgtgc 3240 ttctgtcgat ggtgggcaca gcagtgggaa tgtgtgtgtg cgcacggcgc agatgcatta 3300 caccatatga attaacacca ggagccactg ttcccttcct gctcagcctg ctatgctgcg 3360 tcagaacgac caaggcggcc acatattacg aggctgcggc atatctatgg aacgaacagc 3420 agcccctgtt ctggttgcag gctcttatcc cgctggccgc cttgatcgtc ctgtgcaact 3480 gtctgaaact cttgccatgc tgctgtaaga ccctggcttt tttagccgta atgagcatcg 3540 gtgcccacac tgtgagcgcg tacgaacacg taacagtgat cccgaacacg gtgggagtac 3600 cgtataagac tcttgtcaac agaccgggtt acagccccat ggtgttggag atggagctac 3660 aatcagtcac cttggaacca acactgtcac ttgactacat cacgtgcgag tacaaaactg 3720 tcatcccctc cccgtacgtg aagtgctgtg gtacagcaga gtgcaaggac aagagcctac 3780 cagactacag ctgcaaggtc tttactggag tctacccatt tatgtggggc ggcgcctact 3840 gcttttgcga cgccgaaaat acgcaattga gcgaggcaca tgtagagaaa tctgaatctt 3900 gcaaaacaga gtttgcatcg gcctacagag cccacaccgc atcggcgtcg gcgaagctcc 3960 gcgtccttta ccaaggaaac aacattaccg tagctgccta cgctaacggt gaccatgccg 4020 tcacagtaaa ggacgccaag tttgtcgtgg gcccaatgtc ctccgcctgg acaccttttg 4080 acaacaaaat cgtggtgtac aaaggcgacg tctacaacat ggactaccca ccttttggcg 4140 caggaagacc aggacaattt ggtgacattc aaagtcgtac accggaaagt aaagacgttt 4200 atgccaacac tcagttggta ctacagaggc cagcagcagg cacggtacat gtaccatact 4260 ctcaggcacc atctggcttc aagtattggc tgaaggaacg aggagcatcg ctacagcaca 4320 cggcaccgtt cggttgccag attgcgacaa acccggtaag agctgtaaat tgcgctgtgg 4380 ggaacatacc aatttccatc gacataccgg atgcggcctt tactagggtt gtcgatgcac 4440 cctctgtaac ggacatgtca tgcgaagtac cagcctgcac tcactcctcc gactttgggg 4500 gcgtcgccat catcaaatac acagctagca agaaaggtaa atgtgcagta cattcgatga 4560 ccaacgccgt taccattcga gaagccgacg tagaagtaga ggggaactcc cagctgcaaa 4620 tatccttctc aacagccctg gcaagcgccg agtttcgcgt gcaagtgtgc tccacacaag 4680 tacactgcgc agccgcatgc caccctccaa aggaccacat agtcaattac ccagcatcac 4740 acaccaccct tggggtccag gatatatcca caacggcaat gtcttgggtg cagaagatta 4800 cgggaggagt aggattaatt gttgctgttg ctgccttaat tttaattgtg gtgctatgcg 4860 tgtcgtttag caggcactaa ggatctagat ctgctgtgcc ttctagttgc cagccatctg 4920 ttgtttgccc ctcccccgtg ccttccttga ccctggaagg tgccactccc actgtccttt 4980 cctaataaaa tgaggaaatt gcatcgcatt gtctgagtag gtgtcattct attctggggg 5040 gtggggtggg gcaggacagc aagggggagg attgggaaga caatagcagg catgctgggg 5100 atgcggtggg ctctatggct cgagcatggt catagctgtt tcctgtgtga aattgttatc 5160 cgctcacaat tccacacaac atacgagccg gaagcataaa gtgtaaagcc tggggtgcct 5220 aatgagtgag ctaactcaca ttaattgcgt tgcgctcact gcccgctttc cagtcgggaa 5280 acctgtcgtg ccagctgcat taatgaatcg gccaacgcgc ggggagaggc ggtttgcgta 5340 ttgggcgctc ttccgcttcc tcgctcactg actcgctgcg ctcggtcgtt cggctgcggc 5400 gagcggtatc agctcactca aaggcggtaa tacggttatc cacagaatca ggggataacg 5460 caggaaagaa catgtgagca aaaggccagc aaaaggccag gaaccgtaaa aaggccgcgt 5520 tgctggcgtt tttccatagg ctccgccccc ctgacgagca tcacaaaaat cgacgctcaa 5580 gtcagaggtg gcgaaacccg acaggactat aaagatacca ggcgtttccc cctggaagct 5640 ccctcgtgcg ctctcctgtt ccgaccctgc cgcttaccgg atacctgtcc gcctttctcc 5700 cttcgggaag cgtggcgctt tctcatagct cacgctgtag gtatctcagt tcggtgtagg 5760 tcgttcgctc caagctgggc tgtgtgcacg aaccccccgt tcagcccgac cgctgcgcct 5820 tatccggtaa ctatcgtctt gagtccaacc cggtaagaca cgacttatcg ccactggcag 5880 cagccactgg taacaggatt agcagagcga ggtatgtagg cggtgctaca gagttcttga 5940 agtggtggcc taactacggc tacactagaa gaacagtatt tggtatctgc gctctgctga 6000 agccagttac cttcggaaaa agagttggta gctcttgatc cggcaaacaa accaccgctg 6060 gtagcggtgg tttttttgtt tgcaagcagc agattacgcg cagaaaaaaa ggatctcaag 6120 aagatccttt gatcttttct acggggtctg acgctcagtg gaacgaaaac tcacgttaag 6180 ggattttggt catgagatta tcaaaaagga tcttcaccta gatcctttta aattaaaaat 6240 gaagttttaa atcaatctaa agtatatatg agtaaacttg gtctgacagt tagaaaaact 6300 catcgagcat caaatgaaac tgcaatttat tcatatcagg attatcaata ccatattttt 6360 gaaaaagccg tttctgtaat gaaggagaaa actcaccgag gcagttccat aggatggcaa 6420 gatcctggta tcggtctgcg attccgactc gtccaacatc aatacaacct attaatttcc 6480 cctcgtcaaa aataaggtta tcaagtgaga aatcaccatg agtgacgact gaatccggtg 6540 agaatggcaa aagtttatgc atttctttcc agacttgttc aacaggccag ccattacgct 6600 cgtcatcaaa atcactcgca tcaaccaaac cgttattcat tcgtgattgc gcctgagcga 6660 gacgaaatac gcgatcgctg ttaaaaggac aattacaaac aggaatcgaa tgcaaccggc 6720 gcaggaacac tgccagcgca tcaacaatat tttcacctga atcaggatat tcttctaata 6780 cctggaatgc tgttttccca gggatcgcag tggtgagtaa ccatgcatca tcaggagtac 6840 ggataaaatg cttgatggtc ggaagaggca taaattccgt cagccagttt agtctgacca 6900 tctcatctgt aacatcattg gcaacgctac ctttgccatg tttcagaaac aactctggcg 6960 catcgggctt cccatacaat cgatagattg tcgcacctga ttgcccgaca ttatcgcgag 7020 cccatttata cccatataaa tcagcatcca tgttggaatt taatcgcggc ctagagcaag 7080 acgtttcccg ttgaatatgg ctcatactct tcctttttca atattattga agcatttatc 7140 agggttattg tctcatgagc ggatacatat ttgaatgtat ttagaaaaat aaacaaatag 7200 gggttccgcg cacatttccc cgaaaagtgc cacctgacgt ctaagaaacc attattatca 7260 tgacattaac ctataaaaat aggcgtatca cgaggccctt tcgtc 7305 <210> 39 <211> 1277 <212> PRT <213> Artificial <220> <223> VLP74_15 (CHI VLP 532 NPNAx6) amino acid sequence <400> 39 Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro 1 5 10 15 Arg Pro Trp Ala Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30 Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45 Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60 Arg Lys Asn Lys Lys Gln Arg Gln Lys Lys Gln Ala Pro Gln Asn Asp 65 70 75 80 Pro Lys Gln Lys Lys Gln Pro Pro Gln Lys Lys Pro Ala Gln Lys Lys 85 90 95 Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110 Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Met Gly Tyr Ala Cys 115 120 125 Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140 Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr 145 150 155 160 Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175 Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190 Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205 Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220 Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu 225 230 235 240 Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255 Gly Ala Glu Glu Trp Ser Leu Ala Leu Pro Val Leu Cys Leu Leu Ala 260 265 270 Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285 Glu Lys Glu Pro Glu Ser Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300 Arg Pro Gly Tyr Tyr Gln Leu Leu Lys Ala Ser Leu Thr Cys Ser Pro 305 310 315 320 His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335 Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350 Cys His Ser Pro Ile Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365 Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380 Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Ser His Thr Pro 385 390 395 400 Ala Asp Ala Glu Arg Ala Gly Leu Leu Val Arg Thr Ser Ala Pro Cys 405 410 415 Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430 Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445 Thr Cys Thr His Pro Phe His His Glu Pro Pro Val Ile Gly Arg Glu 450 455 460 Arg Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr 465 470 475 480 Tyr Val Gln Ser Thr Ala Ala Thr Ala Glu Glu Ile Glu Val His Met 485 490 495 Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Thr Gln Gln Ser Gly Asn 500 505 510 Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525 Gly Gly Ser Gly Gly Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 530 535 540 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Gly Gly Ser 545 550 555 560 Asn Glu Gly Leu Thr Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Ile 565 570 575 Asp Gln Cys His Ala Ala Val Thr Asn His Lys Asn Trp Gln Tyr Asn 580 585 590 Ser Pro Leu Val Pro Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys 595 600 605 Ile His Ile Pro Phe Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys 610 615 620 Ala Arg Asn Pro Thr Val Thr Tyr Gly Lys Asn Gln Val Thr Met Leu 625 630 635 640 Leu Tyr Pro Asp His Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Gln 645 650 655 Glu Pro Asn Tyr His Glu Glu Trp Val Thr His Lys Lys Glu Val Thr 660 665 670 Leu Thr Val Pro Thr Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu 675 680 685 Pro Tyr Lys Tyr Trp Pro Gln Met Ser Thr Asn Gly Thr Ala His Gly 690 695 700 His Pro His Glu Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met 705 710 715 720 Thr Val Val Ile Val Ser Val Ala Ser Phe Val Leu Leu Ser Met Val 725 730 735 Gly Thr Ala Val Gly Met Cys Val Cys Ala Arg Arg Arg Cys Ile Thr 740 745 750 Pro Tyr Glu Leu Thr Pro Gly Ala Thr Val Pro Phe Leu Leu Ser Leu 755 760 765 Leu Cys Cys Val Arg Thr Thr Lys Ala Ala Thr Tyr Tyr Glu Ala Ala 770 775 780 Ala Tyr Leu Trp Asn Glu Gln Gln Pro Leu Phe Trp Leu Gln Ala Leu 785 790 795 800 Ile Pro Leu Ala Ala Leu Ile Val Leu Cys Asn Cys Leu Lys Leu Leu 805 810 815 Pro Cys Cys Cys Lys Thr Leu Ala Phe Leu Ala Val Met Ser Ile Gly 820 825 830 Ala His Thr Val Ser Ala Tyr Glu His Val Thr Val Ile Pro Asn Thr 835 840 845 Val Gly Val Pro Tyr Lys Thr Leu Val Asn Arg Pro Gly Tyr Ser Pro 850 855 860 Met Val Leu Glu Met Glu Leu Gln Ser Val Thr Leu Glu Pro Thr Leu 865 870 875 880 Ser Leu Asp Tyr Ile Thr Cys Glu Tyr Lys Thr Val Ile Pro Ser Pro 885 890 895 Tyr Val Lys Cys Cys Gly Thr Ala Glu Cys Lys Asp Lys Ser Leu Pro 900 905 910 Asp Tyr Ser Cys Lys Val Phe Thr Gly Val Tyr Pro Phe Met Trp Gly 915 920 925 Gly Ala Tyr Cys Phe Cys Asp Ala Glu Asn Thr Gln Leu Ser Glu Ala 930 935 940 His Val Glu Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala Ser Ala Tyr 945 950 955 960 Arg Ala His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val Leu Tyr Gln 965 970 975 Gly Asn Asn Ile Thr Val Ala Ala Tyr Ala Asn Gly Asp His Ala Val 980 985 990 Thr Val Lys Asp Ala Lys Phe Val Val Gly Pro Met Ser Ser Ala Trp 995 1000 1005 Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp Val Tyr 1010 1015 1020 Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln Phe 1025 1030 1035 Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr Ala 1040 1045 1050 Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Ala Gly Thr Val His 1055 1060 1065 Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu Lys 1070 1075 1080 Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys Gln 1085 1090 1095 Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly Asn 1100 1105 1110 Ile Pro Ile Ser Ile Asp Ile Pro Asp Ala Ala Phe Thr Arg Val 1115 1120 1125 Val Asp Ala Pro Ser Val Thr Asp Met Ser Cys Glu Val Pro Ala 1130 1135 1140 Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys Tyr 1145 1150 1155 Thr Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr Asn 1160 1165 1170 Ala Val Thr Ile Arg Glu Ala Asp Val Glu Val Glu Gly Asn Ser 1175 1180 1185 Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu Phe 1190 1195 1200 Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Ala Cys 1205 1210 1215 His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His Thr 1220 1225 1230 Thr Leu Gly Val Gln Asp Ile Ser Thr Thr Ala Met Ser Trp Val 1235 1240 1245 Gln Lys Ile Thr Gly Gly Val Gly Leu Ile Val Ala Val Ala Ala 1250 1255 1260 Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1265 1270 1275 <210> 40 <211> 7533 <212> DNA <213> Artificial <220> <223> VLP78_15 (CHI VLP 532 NPNAx25) Whole sequence <400> 40 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240 attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300 tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360 tttcccagtc acgacgttgt aaaacgacgg ccagtgaatt gacgcgtgtt ggcattgatt 420 attgactagt tattaatagt aatcaattac ggggtcatta gttcatagcc catatatgga 480 gttccgcgtt acataactta cggtaaatgg cccgcctggc tgaccgccca acgacccccg 540 cccattgacg tcaataatga cgtatgttcc catagtaacg ccaataggga ctttccattg 600 acgtcaatgg gtggagtatt tacggtaaac tgcccacttg gcagtacatc aagtgtatca 660 tatgccaagt acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct ggcattatgc 720 ccagtacatg accttatggg actttcctac ttggcagtac atctacgtat tagtcatcgc 780 tattaccatg gtgatgcggt tttggcagta catcaatggg cgtggatagc ggtttgactc 840 acggggattt ccaagtctcc accccattga cgtcaatggg agtttgtttt ggcaccaaaa 900 tcaacgggac tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa tgggcggtag 960 gcgtgtacgg tgggaggtct atataagcag agctcgttta gtgaaccgtc agataactgc 1020 aggtcgacga tatcgcggcc gccaccatgg agttcatccc gacgcaaact ttctataaca 1080 gaaggtacca accccgaccc tgggccccac gccctacaat tcaagtaatt agacctagac 1140 cacgtccaca gaggcaggct gggcaactcg cccagctgat ctccgcagtc aacaaattga 1200 ccatgcgcgc ggtacctcaa cagaagcctc gcagaaatcg gaaaaacaag aagcaaaggc 1260 agaagaagca ggcgccgcaa aacgacccaa agcaaaagaa gcaaccacca caaaagaagc 1320 cggctcaaaa gaagaagaaa ccaggccgta gggagagaat gtgcatgaaa attgaaaatg 1380 attgcatctt cgaagtcaag catgaaggca aagtgatggg ctacgcatgc ctggtggggg 1440 ataaagtaat gaaaccagca catgtgaagg gaactatcga caatgccgat ctggctaaac 1500 tggcctttaa gcggtcgtct aaatacgatc ttgaatgtgc acagataccg gtgcacatga 1560 agtctgatgc ctcgaagttt acccacgaga aacccgaggg gtactataac tggcatcacg 1620 gagcagtgca gtattcagga ggccggttca ctatcccgac gggtgcaggc aagccgggag 1680 acagcggcag accgatcttc gacaacaaag gacgggtggt ggccatcgtc ctaggagggg 1740 ccaacgaagg tgcccgcacg gccctctccg tggtgacgtg gaacaaagac atcgtcacaa 1800 aaattacccc tgagggagcc gaagagtgga gcctcgccct cccggtcttg tgcctgttgg 1860 caaacactac attcccctgc tctcagccgc cttgcacacc ctgctgctac gaaaaggaac 1920 cggaaagcac cttgcgcatg cttgaggaca acgtgatgag acccggatac taccagctac 1980 taaaagcatc gctgacttgc tctccccacc gccaaagacg cagtactaag gacaatttta 2040 atgtctataa agccacaaga ccatatctag ctcattgtcc tgactgcgga gaagggcatt 2100 cgtgccacag ccctatcgca ttggagcgca tcagaaatga agcaacggac ggaacgctga 2160 aaatccaggt ctctttgcag atcgggataa agacagatga cagccacgat tggaccaagc 2220 tgcgctatat ggatagccat acgccagcgg acgcggagcg agccggattg cttgtaagga 2280 cttcagcacc gtgcacgatc accgggacca tgggacactt tattctcgcc cgatgcccga 2340 aaggagagac gctgacagtg ggatttacgg acagcagaaa gatcagccac acatgcacac 2400 acccgttcca tcatgaacca cctgtgatag gtagggagag gttccactct cgaccacaac 2460 atggtaaaga gttaccttgc agcacgtacg tgcagagcac cgctgccact gctgaggaga 2520 tagaggtgca tatgccccca gatactcctg accgcacgct gatgacgcag cagtctggca 2580 acgtgaagat cacagttaat gggcagacgg tgcggtacaa gtgcaactgc ggtggctccg 2640 gaggaaaccc gaatgccaat cccaacgcga accccaacgc taaccccaac gccaatccga 2700 atgcaaaccc gaacgttgac ccaaacgcca acccgaatgc caatcccaac gcgaacccca 2760 atgctaaccc aaatgccaac ccaaacgcca accccaacgc taatccaaac gccaacccta 2820 acgccaatcc caacgcgaat cctaacgcta atcccaacgc aaatcccaat gctaatccga 2880 acgcgaaccc taatgcaaac cccaacgcca acccgaacgc taacccgaac gctaatccca 2940 acgccggtgg atccaacgag ggactgacaa ccacagacaa agtgatcaat aactgcaaaa 3000 ttgatcagtg ccatgctgca gtcactaatc acaagaattg gcaatacaac tcccctttag 3060 tcccgcgcaa cgctgaactc ggggaccgta aaggaaagat ccacatccca ttcccattgg 3120 caaacgtgac ttgcagagtg ccaaaagcaa gaaaccctac agtaacttac ggaaaaaacc 3180 aagtcaccat gctgctgtat cctgaccatc cgacactctt gtcttaccgt aacatgggac 3240 aggaaccaaa ttaccacgag gagtgggtga cacacaagaa ggaggttacc ttgaccgtgc 3300 ctactgaggg tctggaggtc acttggggca acaacgaacc atacaagtac tggccgcaga 3360 tgtctacgaa cggtactgct catggtcacc cacatgagat aatcttgtac tattatgagc 3420 tgtaccccac tatgactgta gtcattgtgt cggtggcctc gttcgtgctt ctgtcgatgg 3480 tgggcacagc agtgggaatg tgtgtgtgcg cacggcgcag atgcattaca ccatatgaat 3540 taacaccagg agccactgtt cccttcctgc tcagcctgct atgctgcgtc agaacgacca 3600 aggcggccac atattacgag gctgcggcat atctatggaa cgaacagcag cccctgttct 3660 ggttgcaggc tcttatcccg ctggccgcct tgatcgtcct gtgcaactgt ctgaaactct 3720 tgccatgctg ctgtaagacc ctggcttttt tagccgtaat gagcatcggt gcccacactg 3780 tgagcgcgta cgaacacgta acagtgatcc cgaacacggt gggagtaccg tataagactc 3840 ttgtcaacag accgggttac agccccatgg tgttggagat ggagctacaa tcagtcacct 3900 tggaaccaac actgtcactt gactacatca cgtgcgagta caaaactgtc atcccctccc 3960 cgtacgtgaa gtgctgtggt acagcagagt gcaaggacaa gagcctacca gactacagct 4020 gcaaggtctt tactggagtc tacccattta tgtggggcgg cgcctactgc ttttgcgacg 4080 ccgaaaatac gcaattgagc gaggcacatg tagagaaatc tgaatcttgc aaaacagagt 4140 ttgcatcggc ctacagagcc cacaccgcat cggcgtcggc gaagctccgc gtcctttacc 4200 aaggaaacaa cattaccgta gctgcctacg ctaacggtga ccatgccgtc acagtaaagg 4260 acgccaagtt tgtcgtgggc ccaatgtcct ccgcctggac accttttgac aacaaaatcg 4320 tggtgtacaa aggcgacgtc tacaacatgg actacccacc ttttggcgca ggaagaccag 4380 gacaatttgg tgacattcaa agtcgtacac cggaaagtaa agacgtttat gccaacactc 4440 agttggtact acagaggcca gcagcaggca cggtacatgt accatactct caggcaccat 4500 ctggcttcaa gtattggctg aaggaacgag gagcatcgct acagcacacg gcaccgttcg 4560 gttgccagat tgcgacaaac ccggtaagag ctgtaaattg cgctgtgggg aacataccaa 4620 tttccatcga cataccggat gcggccttta ctagggttgt cgatgcaccc tctgtaacgg 4680 acatgtcatg cgaagtacca gcctgcactc actcctccga ctttgggggc gtcgccatca 4740 tcaaatacac agctagcaag aaaggtaaat gtgcagtaca ttcgatgacc aacgccgtta 4800 ccattcgaga agccgacgta gaagtagagg ggaactccca gctgcaaata tccttctcaa 4860 cagccctggc aagcgccgag tttcgcgtgc aagtgtgctc cacacaagta cactgcgcag 4920 ccgcatgcca ccctccaaag gaccacatag tcaattaccc agcatcacac accacccttg 4980 gggtccagga tatatccaca acggcaatgt cttgggtgca gaagattacg ggaggagtag 5040 gattaattgt tgctgttgct gccttaattt taattgtggt gctatgcgtg tcgtttagca 5100 ggcactaagg atctagatct gctgtgcctt ctagttgcca gccatctgtt gtttgcccct 5160 cccccgtgcc ttccttgacc ctggaaggtg ccactcccac tgtcctttcc taataaaatg 5220 aggaaattgc atcgcattgt ctgagtaggt gtcattctat tctggggggt ggggtggggc 5280 aggacagcaa gggggaggat tgggaagaca atagcaggca tgctggggat gcggtgggct 5340 ctatggctcg agcatggtca tagctgtttc ctgtgtgaaa ttgttatccg ctcacaattc 5400 cacacaacat acgagccgga agcataaagt gtaaagcctg gggtgcctaa tgagtgagct 5460 aactcacatt aattgcgttg cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc 5520 agctgcatta atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctt 5580 ccgcttcctc gctcactgac tcgctgcgct cggtcgttcg gctgcggcga gcggtatcag 5640 ctcactcaaa ggcggtaata cggttatcca cagaatcagg ggataacgca ggaaagaaca 5700 tgtgagcaaa aggccagcaa aaggccagga accgtaaaaa ggccgcgttg ctggcgtttt 5760 tccataggct ccgcccccct gacgagcatc acaaaaatcg acgctcaagt cagaggtggc 5820 gaaacccgac aggactataa agataccagg cgtttccccc tggaagctcc ctcgtgcgct 5880 ctcctgttcc gaccctgccg cttaccggat acctgtccgc ctttctccct tcgggaagcg 5940 tggcgctttc tcatagctca cgctgtaggt atctcagttc ggtgtaggtc gttcgctcca 6000 agctgggctg tgtgcacgaa ccccccgttc agcccgaccg ctgcgcctta tccggtaact 6060 atcgtcttga gtccaacccg gtaagacacg acttatcgcc actggcagca gccactggta 6120 acaggattag cagagcgagg tatgtaggcg gtgctacaga gttcttgaag tggtggccta 6180 actacggcta cactagaaga acagtatttg gtatctgcgc tctgctgaag ccagttacct 6240 tcggaaaaag agttggtagc tcttgatccg gcaaacaaac caccgctggt agcggtggtt 6300 tttttgtttg caagcagcag attacgcgca gaaaaaaagg atctcaagaa gatcctttga 6360 tcttttctac ggggtctgac gctcagtgga acgaaaactc acgttaaggg attttggtca 6420 tgagattatc aaaaaggatc ttcacctaga tccttttaaa ttaaaaatga agttttaaat 6480 caatctaaag tatatatgag taaacttggt ctgacagtta gaaaaactca tcgagcatca 6540 aatgaaactg caatttattc atatcaggat tatcaatacc atatttttga aaaagccgtt 6600 tctgtaatga aggagaaaac tcaccgaggc agttccatag gatggcaaga tcctggtatc 6660 ggtctgcgat tccgactcgt ccaacatcaa tacaacctat taatttcccc tcgtcaaaaa 6720 taaggttatc aagtgagaaa tcaccatgag tgacgactga atccggtgag aatggcaaaa 6780 gtttatgcat ttctttccag acttgttcaa caggccagcc attacgctcg tcatcaaaat 6840 cactcgcatc aaccaaaccg ttattcattc gtgattgcgc ctgagcgaga cgaaatacgc 6900 gatcgctgtt aaaaggacaa ttacaaacag gaatcgaatg caaccggcgc aggaacactg 6960 ccagcgcatc aacaatattt tcacctgaat caggatattc ttctaatacc tggaatgctg 7020 ttttcccagg gatcgcagtg gtgagtaacc atgcatcatc aggagtacgg ataaaatgct 7080 tgatggtcgg aagaggcata aattccgtca gccagtttag tctgaccatc tcatctgtaa 7140 catcattggc aacgctacct ttgccatgtt tcagaaacaa ctctggcgca tcgggcttcc 7200 catacaatcg atagattgtc gcacctgatt gcccgacatt atcgcgagcc catttatacc 7260 catataaatc agcatccatg ttggaattta atcgcggcct agagcaagac gtttcccgtt 7320 gaatatggct catactcttc ctttttcaat attattgaag catttatcag ggttattgtc 7380 tcatgagcgg atacatattt gaatgtattt agaaaaataa acaaataggg gttccgcgca 7440 catttccccg aaaagtgcca cctgacgtct aagaaaccat tattatcatg acattaacct 7500 ataaaaatag gcgtatcacg aggccctttc gtc 7533 <210> 41 <211> 1353 <212> PRT <213> Artificial <220> <223> VLP78_15 (CHI VLP 532 NPNAx25) amino acid sequence <400> 41 Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro 1 5 10 15 Arg Pro Trp Ala Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30 Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45 Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60 Arg Lys Asn Lys Lys Gln Arg Gln Lys Lys Gln Ala Pro Gln Asn Asp 65 70 75 80 Pro Lys Gln Lys Lys Gln Pro Pro Gln Lys Lys Pro Ala Gln Lys Lys 85 90 95 Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110 Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Met Gly Tyr Ala Cys 115 120 125 Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140 Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr 145 150 155 160 Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175 Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190 Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205 Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220 Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu 225 230 235 240 Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255 Gly Ala Glu Glu Trp Ser Leu Ala Leu Pro Val Leu Cys Leu Leu Ala 260 265 270 Asn Thr Thr Phe Pro Cys Ser Gln Pro Pro Cys Thr Pro Cys Cys Tyr 275 280 285 Glu Lys Glu Pro Glu Ser Thr Leu Arg Met Leu Glu Asp Asn Val Met 290 295 300 Arg Pro Gly Tyr Tyr Gln Leu Leu Lys Ala Ser Leu Thr Cys Ser Pro 305 310 315 320 His Arg Gln Arg Arg Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala 325 330 335 Thr Arg Pro Tyr Leu Ala His Cys Pro Asp Cys Gly Glu Gly His Ser 340 345 350 Cys His Ser Pro Ile Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp 355 360 365 Gly Thr Leu Lys Ile Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp 370 375 380 Asp Ser His Asp Trp Thr Lys Leu Arg Tyr Met Asp Ser His Thr Pro 385 390 395 400 Ala Asp Ala Glu Arg Ala Gly Leu Leu Val Arg Thr Ser Ala Pro Cys 405 410 415 Thr Ile Thr Gly Thr Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys 420 425 430 Gly Glu Thr Leu Thr Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His 435 440 445 Thr Cys Thr His Pro Phe His His Glu Pro Pro Val Ile Gly Arg Glu 450 455 460 Arg Phe His Ser Arg Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr 465 470 475 480 Tyr Val Gln Ser Thr Ala Ala Thr Ala Glu Glu Ile Glu Val His Met 485 490 495 Pro Pro Asp Thr Pro Asp Arg Thr Leu Met Thr Gln Gln Ser Gly Asn 500 505 510 Val Lys Ile Thr Val Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys 515 520 525 Gly Gly Ser Gly Gly Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 530 535 540 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Val Asp Pro Asn 545 550 555 560 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 565 570 575 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 580 585 590 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 595 600 605 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 610 615 620 Ala Asn Pro Asn Ala Asn Pro Asn Ala Gly Gly Ser Asn Glu Gly Leu 625 630 635 640 Thr Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Ile Asp Gln Cys His 645 650 655 Ala Ala Val Thr Asn His Lys Asn Trp Gln Tyr Asn Ser Pro Leu Val 660 665 670 Pro Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile Pro 675 680 685 Phe Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn Pro 690 695 700 Thr Val Thr Tyr Gly Lys Asn Gln Val Thr Met Leu Leu Tyr Pro Asp 705 710 715 720 His Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Gln Glu Pro Asn Tyr 725 730 735 His Glu Glu Trp Val Thr His Lys Lys Glu Val Thr Leu Thr Val Pro 740 745 750 Thr Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys Tyr 755 760 765 Trp Pro Gln Met Ser Thr Asn Gly Thr Ala His Gly His Pro His Glu 770 775 780 Ile Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr Val Val Ile 785 790 795 800 Val Ser Val Ala Ser Phe Val Leu Leu Ser Met Val Gly Thr Ala Val 805 810 815 Gly Met Cys Val Cys Ala Arg Arg Arg Cys Ile Thr Pro Tyr Glu Leu 820 825 830 Thr Pro Gly Ala Thr Val Pro Phe Leu Leu Ser Leu Leu Cys Cys Val 835 840 845 Arg Thr Thr Lys Ala Ala Thr Tyr Tyr Glu Ala Ala Ala Tyr Leu Trp 850 855 860 Asn Glu Gln Gln Pro Leu Phe Trp Leu Gln Ala Leu Ile Pro Leu Ala 865 870 875 880 Ala Leu Ile Val Leu Cys Asn Cys Leu Lys Leu Leu Pro Cys Cys Cys 885 890 895 Lys Thr Leu Ala Phe Leu Ala Val Met Ser Ile Gly Ala His Thr Val 900 905 910 Ser Ala Tyr Glu His Val Thr Val Ile Pro Asn Thr Val Gly Val Pro 915 920 925 Tyr Lys Thr Leu Val Asn Arg Pro Gly Tyr Ser Pro Met Val Leu Glu 930 935 940 Met Glu Leu Gln Ser Val Thr Leu Glu Pro Thr Leu Ser Leu Asp Tyr 945 950 955 960 Ile Thr Cys Glu Tyr Lys Thr Val Ile Pro Ser Pro Tyr Val Lys Cys 965 970 975 Cys Gly Thr Ala Glu Cys Lys Asp Lys Ser Leu Pro Asp Tyr Ser Cys 980 985 990 Lys Val Phe Thr Gly Val Tyr Pro Phe Met Trp Gly Gly Ala Tyr Cys 995 1000 1005 Phe Cys Asp Ala Glu Asn Thr Gln Leu Ser Glu Ala His Val Glu 1010 1015 1020 Lys Ser Glu Ser Cys Lys Thr Glu Phe Ala Ser Ala Tyr Arg Ala 1025 1030 1035 His Thr Ala Ser Ala Ser Ala Lys Leu Arg Val Leu Tyr Gln Gly 1040 1045 1050 Asn Asn Ile Thr Val Ala Ala Tyr Ala Asn Gly Asp His Ala Val 1055 1060 1065 Thr Val Lys Asp Ala Lys Phe Val Val Gly Pro Met Ser Ser Ala 1070 1075 1080 Trp Thr Pro Phe Asp Asn Lys Ile Val Val Tyr Lys Gly Asp Val 1085 1090 1095 Tyr Asn Met Asp Tyr Pro Pro Phe Gly Ala Gly Arg Pro Gly Gln 1100 1105 1110 Phe Gly Asp Ile Gln Ser Arg Thr Pro Glu Ser Lys Asp Val Tyr 1115 1120 1125 Ala Asn Thr Gln Leu Val Leu Gln Arg Pro Ala Ala Gly Thr Val 1130 1135 1140 His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe Lys Tyr Trp Leu 1145 1150 1155 Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro Phe Gly Cys 1160 1165 1170 Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala Val Gly 1175 1180 1185 Asn Ile Pro Ile Ser Ile Asp Ile Pro Asp Ala Ala Phe Thr Arg 1190 1195 1200 Val Val Asp Ala Pro Ser Val Thr Asp Met Ser Cys Glu Val Pro 1205 1210 1215 Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys 1220 1225 1230 Tyr Thr Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr 1235 1240 1245 Asn Ala Val Thr Ile Arg Glu Ala Asp Val Glu Val Glu Gly Asn 1250 1255 1260 Ser Gln Leu Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu 1265 1270 1275 Phe Arg Val Gln Val Cys Ser Thr Gln Val His Cys Ala Ala Ala 1280 1285 1290 Cys His Pro Pro Lys Asp His Ile Val Asn Tyr Pro Ala Ser His 1295 1300 1305 Thr Thr Leu Gly Val Gln Asp Ile Ser Thr Thr Ala Met Ser Trp 1310 1315 1320 Val Gln Lys Ile Thr Gly Gly Val Gly Leu Ile Val Ala Val Ala 1325 1330 1335 Ala Leu Ile Leu Ile Val Val Leu Cys Val Ser Phe Ser Arg His 1340 1345 1350 <210> 42 <211> 7329 <212> DNA <213> Artificial <220> <223> VLP74_25 (VEEV VLP 519 NPNAx6) Whole sequence <400> 42 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240 attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300 tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360 tttcccagtc acgacgttgt aaaacgacgg ccagtgaatt gacgcgtgtt ggcattgatt 420 attgactagt tattaatagt aatcaattac ggggtcatta gttcatagcc catatatgga 480 gttccgcgtt acataactta cggtaaatgg cccgcctggc tgaccgccca acgacccccg 540 cccattgacg tcaataatga cgtatgttcc catagtaacg ccaataggga ctttccattg 600 acgtcaatgg gtggagtatt tacggtaaac tgcccacttg gcagtacatc aagtgtatca 660 tatgccaagt acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct ggcattatgc 720 ccagtacatg accttatggg actttcctac ttggcagtac atctacgtat tagtcatcgc 780 tattaccatg gtgatgcggt tttggcagta catcaatggg cgtggatagc ggtttgactc 840 acggggattt ccaagtctcc accccattga cgtcaatggg agtttgtttt ggcaccaaaa 900 tcaacgggac tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa tgggcggtag 960 gcgtgtacgg tgggaggtct atataagcag agctcgttta gtgaaccgtc agataactgc 1020 aggtcgacga tatcgcggcc gccaccatgt tcccgttcca gccaatgtat ccgatgcagc 1080 caatgcccta tcgcaacccg ttcgcggccc cgcgcaggcc ctggttcccc agaaccgacc 1140 cttttctggc gatgcaggtg caggaattaa cccgctcgat ggctaacctg acgttcaagc 1200 aacgccggga cgcgccacct gaggggccat ccgctaataa accgaagaag gaggcctcgc 1260 aaaaacagaa agggggaggc caagggaaga agaagaagaa ccaagggaag aagaaggcta 1320 agacagggcc gcctaatccg aaggcacaga atggaaacaa gaagaagacc aacaagaaac 1380 caggcaagag acagcgcatg gtcatgaaat tggaatctga caagacgttc ccaatcatgt 1440 tggaagggaa gataaacggc tacgcttgtg tggtcggagg gaagttattc aggccgatgc 1500 atgtggaagg caagatcgac aacgacgttc tggccgcgct taagacgaag aaagcatcca 1560 aatacgatct tgagtatgca gatgtgccac agaacatgcg ggccgataca ttcaaataca 1620 cccatgagaa accccaaggc tattacagct ggcatcatgg agcagtccaa tatgaaaatg 1680 ggcgtttcac ggtgccgaaa ggagttgggg ccaagggaga cagcggacga cccattctgg 1740 ataaccaggg acgggtggtc gctattgtgc tgggaggtgt gaatgaagga tctaggacag 1800 ccctttcagt cgtcatgtgg aacgagaagg gagttaccgt gaagtatact ccagagaact 1860 gcgagcaatg gtcactagtg accaccatgt gtctgctcgc caatgtgacg ttcccatgtg 1920 ctcaaccacc aatttgctac gacagaaaac cagcagagac tttggccatg ctcagcgtta 1980 acgttgacaa cccgggctac gatgagctgc tggaagcagc tgttaagtgc cccggaagga 2040 aaaggagatc caccgaggag ctgtttaatg agtataagct aacgcgccct tacatggcca 2100 gatgcatcag atgtgcagtt gggagctgcc atagtccaat agcaatcgag gcagtaaaga 2160 gcgacgggca cgacggttat gttagacttc agacttcctc gcagtatggc ctggattcct 2220 ccggcaactt aaagggcagg accatgcggt atgacatgca cgggaccatt aaagagatac 2280 cactacatca agtgtcactc tatacatctc gcccgtgtca cattgtggat gggcacggtt 2340 atttcctgct tgccaggtgc ccggcagggg actccatcac catggaattt aagaaagatt 2400 ccgtcagaca ctcctgctcg gtgccgtatg aagtgaaatt taatcctgta ggcagagaac 2460 tctatactca tcccccagaa cacggagtag agcaagcgtg ccaagtctac gcacatgatg 2520 cacagaacag aggagcttat gtcgagatgc acctcccggg ctcagaagtg gacagcagtt 2580 tggtttcctt gagcggcagt tccggaggaa acccgaatgc caatcccaac gcgaacccca 2640 atgctaaccc aaatgccaac ccaaacgcca accccaacgc tggtggatcc tcagtcaccg 2700 tgacacctcc tgatgggact agcgccctgg tggaatgcga gtgtggcggc acaaagatct 2760 ccgagaccat caacaagaca aaacagttca gccagtgcac aaagaaggag cagtgcagag 2820 catatcggct gcagaacgat aagtgggtgt ataattctga caaactgccc aaagcagcgg 2880 gagccacctt aaaaggaaaa ctgcatgtcc cattcttgct ggcagacggc aaatgcaccg 2940 tgcctctagc accagaacct atgataacct tcggtttcag atcagtgtca ctgaaactgc 3000 accctaagaa tcccacatat ctaatcaccc gccaacttgc tgatgagcct cactacacgc 3060 acgagctcat atctgaacca gctgttagga attttaccgt caccgaaaaa gggtgggagt 3120 ttgtatgggg aaaccacccg ccgaaaaggt tttgggcaca ggaaacagca cccggaaatc 3180 cacatgggct accgcacgag gtgataactc attattacca cagataccct atgtccacca 3240 tcctgggttt gtcaatttgt gccgccattg caaccgtttc cgttgcagcg tctacctggc 3300 tgttttgcag atcaagagtt gcgtgcctaa ctccttaccg gctaacacct aacgctagga 3360 taccattttg tctggctgtg ctttgctgcg cccgcactgc ccgggccgag accacctggg 3420 agtccttgga tcacctatgg aacaataacc aacagatgtt ctggattcaa ttgctgatcc 3480 ctctggccgc cttgatcgta gtgactcgcc tgctcaggtg cgtgtgctgt gtcgtgcctt 3540 ttttagtcat ggccggcgcc gcaggcgccg gcgcctacga gcacgcgacc acgatgccga 3600 gccaagcggg aatctcgtat aacactatag tcaacagagc aggctacgca ccactcccta 3660 tcagcataac accaacaaag atcaagctga tacctacagt gaacttggag tacgtcacct 3720 gccactacaa aacaggaatg gattcaccag ccatcaaatg ctgcggatct caggaatgca 3780 ctccaactta caggcctgat gaacagtgca aagtcttcac aggggtttac ccgttcatgt 3840 ggggtggtgc atattgcttt tgcgacactg agaacaccca agtcagcaag gcctacgtaa 3900 tgaaatctga cgactgcctt gcggatcatg ctgaagcata taaagcgcac acagcctcag 3960 tgcaggcgtt cctcaacatc acagtgggag aacactctat tgtgactacc gtgtatgtga 4020 atggagaaac tcctgtgaat ttcaatgggg tcaaaataac tgcaggtccg ctttccacag 4080 cttggacacc ctttgatcgc aaaatcgtgc agtatgccgg ggagatatat aattatgatt 4140 ttcctgagta tggggcagga caaccaggag catttggaga tatacaatcc agaacagtct 4200 caagctctga tctgtatgcc aataccaacc tagtgctgca gagacccaaa gcaggagcga 4260 tccacgtgcc atacactcag gcaccttcgg gttttgagca atggaagaaa gataaagctc 4320 catcattgaa atttaccgcc cctttcggat gcgaaatata tacaaacccc attcgcgccg 4380 aaaactgtgc tgtagggtca attccattag cctttgacat tcccgacgcc ttgttcacca 4440 gggtgtcaga aacaccgaca ctttcagcgg ccgaatgcac tcttaacgag tgcgtgtatt 4500 cttccgactt tggtgggatc gccacggtca agtactcggc cagcaagtca ggcaagtgcg 4560 cagtccatgt gccatcaggg actgctaccc taaaagaagc agcagtcgag ctaaccgagc 4620 aagggtcggc gactatccat ttctcgaccg caaatatcca cccggagttc aggctccaaa 4680 tatgcacatc atatgttacg tgcaaaggtg attgtcaccc cccgaaagac catattgtga 4740 cacaccctca gtatcacgcc caaacattta cagccgcggt gtcaaaaacc gcgtggacgt 4800 ggttaacatc cctgctggga ggatcagccg taattattat aattggcttg gtgctggcta 4860 ctattgtggc catgtacgtg ctgaccaacc agaaacataa ttaaggatct agatctgctg 4920 tgccttctag ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg 4980 aaggtgccac tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga 5040 gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg 5100 aagacaatag caggcatgct ggggatgcgg tgggctctat ggctcgagca tggtcatagc 5160 tgtttcctgt gtgaaattgt tatccgctca caattccaca caacatacga gccggaagca 5220 taaagtgtaa agcctggggt gcctaatgag tgagctaact cacattaatt gcgttgcgct 5280 cactgcccgc tttccagtcg ggaaacctgt cgtgccagct gcattaatga atcggccaac 5340 gcgcggggag aggcggtttg cgtattgggc gctcttccgc ttcctcgctc actgactcgc 5400 tgcgctcggt cgttcggctg cggcgagcgg tatcagctca ctcaaaggcg gtaatacggt 5460 tatccacaga atcaggggat aacgcaggaa agaacatgtg agcaaaaggc cagcaaaagg 5520 ccaggaaccg taaaaaggcc gcgttgctgg cgtttttcca taggctccgc ccccctgacg 5580 agcatcacaa aaatcgacgc tcaagtcaga ggtggcgaaa cccgacagga ctataaagat 5640 accaggcgtt tccccctgga agctccctcg tgcgctctcc tgttccgacc ctgccgctta 5700 ccggatacct gtccgccttt ctcccttcgg gaagcgtggc gctttctcat agctcacgct 5760 gtaggtatct cagttcggtg taggtcgttc gctccaagct gggctgtgtg cacgaacccc 5820 ccgttcagcc cgaccgctgc gccttatccg gtaactatcg tcttgagtcc aacccggtaa 5880 gacacgactt atcgccactg gcagcagcca ctggtaacag gattagcaga gcgaggtatg 5940 taggcggtgc tacagagttc ttgaagtggt ggcctaacta cggctacact agaagaacag 6000 tatttggtat ctgcgctctg ctgaagccag ttaccttcgg aaaaagagtt ggtagctctt 6060 gatccggcaa acaaaccacc gctggtagcg gtggtttttt tgtttgcaag cagcagatta 6120 cgcgcagaaa aaaaggatct caagaagatc ctttgatctt ttctacgggg tctgacgctc 6180 agtggaacga aaactcacgt taagggattt tggtcatgag attatcaaaa aggatcttca 6240 cctagatcct tttaaattaa aaatgaagtt ttaaatcaat ctaaagtata tatgagtaaa 6300 cttggtctga cagttagaaa aactcatcga gcatcaaatg aaactgcaat ttattcatat 6360 caggattatc aataccatat ttttgaaaaa gccgtttctg taatgaagga gaaaactcac 6420 cgaggcagtt ccataggatg gcaagatcct ggtatcggtc tgcgattccg actcgtccaa 6480 catcaataca acctattaat ttcccctcgt caaaaataag gttatcaagt gagaaatcac 6540 catgagtgac gactgaatcc ggtgagaatg gcaaaagttt atgcatttct ttccagactt 6600 gttcaacagg ccagccatta cgctcgtcat caaaatcact cgcatcaacc aaaccgttat 6660 tcattcgtga ttgcgcctga gcgagacgaa atacgcgatc gctgttaaaa ggacaattac 6720 aaacaggaat cgaatgcaac cggcgcagga acactgccag cgcatcaaca atattttcac 6780 ctgaatcagg atattcttct aatacctgga atgctgtttt cccagggatc gcagtggtga 6840 gtaaccatgc atcatcagga gtacggataa aatgcttgat ggtcggaaga ggcataaatt 6900 ccgtcagcca gtttagtctg accatctcat ctgtaacatc attggcaacg ctacctttgc 6960 catgtttcag aaacaactct ggcgcatcgg gcttcccata caatcgatag attgtcgcac 7020 ctgattgccc gacattatcg cgagcccatt tatacccata taaatcagca tccatgttgg 7080 aatttaatcg cggcctagag caagacgttt cccgttgaat atggctcata ctcttccttt 7140 ttcaatatta ttgaagcatt tatcagggtt attgtctcat gagcggatac atatttgaat 7200 gtatttagaa aaataaacaa ataggggttc cgcgcacatt tccccgaaaa gtgccacctg 7260 acgtctaaga aaccattatt atcatgacat taacctataa aaataggcgt atcacgaggc 7320 cctttcgtc 7329 <210> 43 <211> 1285 <212> PRT <213> Artificial <220> <223> VLP74_25 (VEEV VLP 519 NPNAx6) amino acid sequence <400> 43 Met Phe Pro Phe Gln Pro Met Tyr Pro Met Gln Pro Met Pro Tyr Arg 1 5 10 15 Asn Pro Phe Ala Ala Pro Arg Arg Pro Trp Phe Pro Arg Thr Asp Pro 20 25 30 Phe Leu Ala Met Gln Val Gln Glu Leu Thr Arg Ser Met Ala Asn Leu 35 40 45 Thr Phe Lys Gln Arg Arg Asp Ala Pro Pro Glu Gly Pro Ser Ala Asn 50 55 60 Lys Pro Lys Lys Glu Ala Ser Gln Lys Gln Lys Gly Gly Gly Gln Gly 65 70 75 80 Lys Lys Lys Lys Asn Gln Gly Lys Lys Lys Ala Lys Thr Gly Pro Pro 85 90 95 Asn Pro Lys Ala Gln Asn Gly Asn Lys Lys Lys Thr Asn Lys Lys Pro 100 105 110 Gly Lys Arg Gln Arg Met Val Met Lys Leu Glu Ser Asp Lys Thr Phe 115 120 125 Pro Ile Met Leu Glu Gly Lys Ile Asn Gly Tyr Ala Cys Val Val Gly 130 135 140 Gly Lys Leu Phe Arg Pro Met His Val Glu Gly Lys Ile Asp Asn Asp 145 150 155 160 Val Leu Ala Ala Leu Lys Thr Lys Lys Ala Ser Lys Tyr Asp Leu Glu 165 170 175 Tyr Ala Asp Val Pro Gln Asn Met Arg Ala Asp Thr Phe Lys Tyr Thr 180 185 190 His Glu Lys Pro Gln Gly Tyr Tyr Ser Trp His His Gly Ala Val Gln 195 200 205 Tyr Glu Asn Gly Arg Phe Thr Val Pro Lys Gly Val Gly Ala Lys Gly 210 215 220 Asp Ser Gly Arg Pro Ile Leu Asp Asn Gln Gly Arg Val Val Ala Ile 225 230 235 240 Val Leu Gly Gly Val Asn Glu Gly Ser Arg Thr Ala Leu Ser Val Val 245 250 255 Met Trp Asn Glu Lys Gly Val Thr Val Lys Tyr Thr Pro Glu Asn Cys 260 265 270 Glu Gln Trp Ser Leu Val Thr Thr Met Cys Leu Leu Ala Asn Val Thr 275 280 285 Phe Pro Cys Ala Gln Pro Pro Ile Cys Tyr Asp Arg Lys Pro Ala Glu 290 295 300 Thr Leu Ala Met Leu Ser Val Asn Val Asp Asn Pro Gly Tyr Asp Glu 305 310 315 320 Leu Leu Glu Ala Ala Val Lys Cys Pro Gly Arg Lys Arg Arg Ser Thr 325 330 335 Glu Glu Leu Phe Asn Glu Tyr Lys Leu Thr Arg Pro Tyr Met Ala Arg 340 345 350 Cys Ile Arg Cys Ala Val Gly Ser Cys His Ser Pro Ile Ala Ile Glu 355 360 365 Ala Val Lys Ser Asp Gly His Asp Gly Tyr Val Arg Leu Gln Thr Ser 370 375 380 Ser Gln Tyr Gly Leu Asp Ser Ser Gly Asn Leu Lys Gly Arg Thr Met 385 390 395 400 Arg Tyr Asp Met His Gly Thr Ile Lys Glu Ile Pro Leu His Gln Val 405 410 415 Ser Leu Tyr Thr Ser Arg Pro Cys His Ile Val Asp Gly His Gly Tyr 420 425 430 Phe Leu Leu Ala Arg Cys Pro Ala Gly Asp Ser Ile Thr Met Glu Phe 435 440 445 Lys Lys Asp Ser Val Arg His Ser Cys Ser Val Pro Tyr Glu Val Lys 450 455 460 Phe Asn Pro Val Gly Arg Glu Leu Tyr Thr His Pro Pro Glu His Gly 465 470 475 480 Val Glu Gln Ala Cys Gln Val Tyr Ala His Asp Ala Gln Asn Arg Gly 485 490 495 Ala Tyr Val Glu Met His Leu Pro Gly Ser Glu Val Asp Ser Ser Leu 500 505 510 Val Ser Leu Ser Gly Ser Ser Gly Gly Asn Pro Asn Ala Asn Pro Asn 515 520 525 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 530 535 540 Ala Gly Gly Ser Ser Val Thr Val Thr Pro Pro Asp Gly Thr Ser Ala 545 550 555 560 Leu Val Glu Cys Glu Cys Gly Gly Thr Lys Ile Ser Glu Thr Ile Asn 565 570 575 Lys Thr Lys Gln Phe Ser Gln Cys Thr Lys Lys Glu Gln Cys Arg Ala 580 585 590 Tyr Arg Leu Gln Asn Asp Lys Trp Val Tyr Asn Ser Asp Lys Leu Pro 595 600 605 Lys Ala Ala Gly Ala Thr Leu Lys Gly Lys Leu His Val Pro Phe Leu 610 615 620 Leu Ala Asp Gly Lys Cys Thr Val Pro Leu Ala Pro Glu Pro Met Ile 625 630 635 640 Thr Phe Gly Phe Arg Ser Val Ser Leu Lys Leu His Pro Lys Asn Pro 645 650 655 Thr Tyr Leu Ile Thr Arg Gln Leu Ala Asp Glu Pro His Tyr Thr His 660 665 670 Glu Leu Ile Ser Glu Pro Ala Val Arg Asn Phe Thr Val Thr Glu Lys 675 680 685 Gly Trp Glu Phe Val Trp Gly Asn His Pro Pro Lys Arg Phe Trp Ala 690 695 700 Gln Glu Thr Ala Pro Gly Asn Pro His Gly Leu Pro His Glu Val Ile 705 710 715 720 Thr His Tyr Tyr His Arg Tyr Pro Met Ser Thr Ile Leu Gly Leu Ser 725 730 735 Ile Cys Ala Ala Ile Ala Thr Val Ser Val Ala Ala Ser Thr Trp Leu 740 745 750 Phe Cys Arg Ser Arg Val Ala Cys Leu Thr Pro Tyr Arg Leu Thr Pro 755 760 765 Asn Ala Arg Ile Pro Phe Cys Leu Ala Val Leu Cys Cys Ala Arg Thr 770 775 780 Ala Arg Ala Glu Thr Thr Trp Glu Ser Leu Asp His Leu Trp Asn Asn 785 790 795 800 Asn Gln Gln Met Phe Trp Ile Gln Leu Leu Ile Pro Leu Ala Ala Leu 805 810 815 Ile Val Val Thr Arg Leu Leu Arg Cys Val Cys Cys Val Val Pro Phe 820 825 830 Leu Val Met Ala Gly Ala Ala Gly Ala Gly Ala Tyr Glu His Ala Thr 835 840 845 Thr Met Pro Ser Gln Ala Gly Ile Ser Tyr Asn Thr Ile Val Asn Arg 850 855 860 Ala Gly Tyr Ala Pro Leu Pro Ile Ser Ile Thr Pro Thr Lys Ile Lys 865 870 875 880 Leu Ile Pro Thr Val Asn Leu Glu Tyr Val Thr Cys His Tyr Lys Thr 885 890 895 Gly Met Asp Ser Pro Ala Ile Lys Cys Cys Gly Ser Gln Glu Cys Thr 900 905 910 Pro Thr Tyr Arg Pro Asp Glu Gln Cys Lys Val Phe Thr Gly Val Tyr 915 920 925 Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe Cys Asp Thr Glu Asn Thr 930 935 940 Gln Val Ser Lys Ala Tyr Val Met Lys Ser Asp Asp Cys Leu Ala Asp 945 950 955 960 His Ala Glu Ala Tyr Lys Ala His Thr Ala Ser Val Gln Ala Phe Leu 965 970 975 Asn Ile Thr Val Gly Glu His Ser Ile Val Thr Thr Val Tyr Val Asn 980 985 990 Gly Glu Thr Pro Val Asn Phe Asn Gly Val Lys Ile Thr Ala Gly Pro 995 1000 1005 Leu Ser Thr Ala Trp Thr Pro Phe Asp Arg Lys Ile Val Gln Tyr 1010 1015 1020 Ala Gly Glu Ile Tyr Asn Tyr Asp Phe Pro Glu Tyr Gly Ala Gly 1025 1030 1035 Gln Pro Gly Ala Phe Gly Asp Ile Gln Ser Arg Thr Val Ser Ser 1040 1045 1050 Ser Asp Leu Tyr Ala Asn Thr Asn Leu Val Leu Gln Arg Pro Lys 1055 1060 1065 Ala Gly Ala Ile His Val Pro Tyr Thr Gln Ala Pro Ser Gly Phe 1070 1075 1080 Glu Gln Trp Lys Lys Asp Lys Ala Pro Ser Leu Lys Phe Thr Ala 1085 1090 1095 Pro Phe Gly Cys Glu Ile Tyr Thr Asn Pro Ile Arg Ala Glu Asn 1100 1105 1110 Cys Ala Val Gly Ser Ile Pro Leu Ala Phe Asp Ile Pro Asp Ala 1115 1120 1125 Leu Phe Thr Arg Val Ser Glu Thr Pro Thr Leu Ser Ala Ala Glu 1130 1135 1140 Cys Thr Leu Asn Glu Cys Val Tyr Ser Ser Asp Phe Gly Gly Ile 1145 1150 1155 Ala Thr Val Lys Tyr Ser Ala Ser Lys Ser Gly Lys Cys Ala Val 1160 1165 1170 His Val Pro Ser Gly Thr Ala Thr Leu Lys Glu Ala Ala Val Glu 1175 1180 1185 Leu Thr Glu Gln Gly Ser Ala Thr Ile His Phe Ser Thr Ala Asn 1190 1195 1200 Ile His Pro Glu Phe Arg Leu Gln Ile Cys Thr Ser Tyr Val Thr 1205 1210 1215 Cys Lys Gly Asp Cys His Pro Pro Lys Asp His Ile Val Thr His 1220 1225 1230 Pro Gln Tyr His Ala Gln Thr Phe Thr Ala Ala Val Ser Lys Thr 1235 1240 1245 Ala Trp Thr Trp Leu Thr Ser Leu Leu Gly Gly Ser Ala Val Ile 1250 1255 1260 Ile Ile Ile Gly Leu Val Leu Ala Thr Ile Val Ala Met Tyr Val 1265 1270 1275 Leu Thr Asn Gln Lys His Asn 1280 1285 <210> 44 <211> 20 <212> PRT <213> Plasmodium falciparum <400> 44 Glu Tyr Leu Asn Lys Ile Gln Asn Ser Leu Ser Thr Glu Trp Ser Pro 1 5 10 15 Cys Ser Val Thr 20 <210> 45 <211> 20 <212> PRT <213> Plasmodium yoelii <400> 45 Tyr Asn Arg Asn Ile Val Asn Arg Leu Leu Gly Asp Ala Leu Asn Gly 1 5 10 15 Pro Glu Glu Lys 20 <210> 46 <211> 30 <212> PRT <213> Artificial <220> <223> VLP74 insert <400> 46 Ser Gly Gly Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn 1 5 10 15 Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Gly Gly Ser 20 25 30 <210> 47 <211> 90 <212> DNA <213> Artificial <220> <223> VLP74 insert <400> 47 tccggaggaa acccgaatgc caatcccaac gcgaacccca atgctaaccc aaatgccaac 60 ccaaacgcca accccaacgc tggtggatcc 90 <210> 48 <211> 106 <212> PRT <213> Artificial <220> <223> VLP78 insert <400> 48 Ser Gly Gly Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn 1 5 10 15 Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Val Asp Pro Asn Ala Asn 20 25 30 Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn 35 40 45 Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn 50 55 60 Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn 65 70 75 80 Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn 85 90 95 Pro Asn Ala Asn Pro Asn Ala Gly Gly Ser 100 105 <210> 49 <211> 318 <212> DNA <213> Artificial <220> <223> VLP74 insert <400> 49 tccggaggaa acccgaatgc caatcccaac gcgaacccca acgctaaccc caacgccaat 60 ccgaatgcaa acccgaacgt tgacccaaac gccaacccga atgccaatcc caacgcgaac 120 cccaatgcta acccaaatgc caacccaaac gccaacccca acgctaatcc aaacgccaac 180 cctaacgcca atcccaacgc gaatcctaac gctaatccca acgcaaatcc caatgctaat 240 ccgaacgcga accctaatgc aaaccccaac gccaacccga acgctaaccc gaacgctaat 300 cccaacgccg gtggatcc 318 <210> 50 <211> 452 <212> PRT <213> Artificial <220> <223> CHIKV E2-74 fusion protein <400> 50 Ser Thr Lys Asp Asn Phe Asn Val Tyr Lys Ala Thr Arg Pro Tyr Leu 1 5 10 15 Ala His Cys Pro Asp Cys Gly Glu Gly His Ser Cys His Ser Pro Ile 20 25 30 Ala Leu Glu Arg Ile Arg Asn Glu Ala Thr Asp Gly Thr Leu Lys Ile 35 40 45 Gln Val Ser Leu Gln Ile Gly Ile Lys Thr Asp Asp Ser His Asp Trp 50 55 60 Thr Lys Leu Arg Tyr Met Asp Ser His Thr Pro Ala Asp Ala Glu Arg 65 70 75 80 Ala Gly Leu Leu Val Arg Thr Ser Ala Pro Cys Thr Ile Thr Gly Thr 85 90 95 Met Gly His Phe Ile Leu Ala Arg Cys Pro Lys Gly Glu Thr Leu Thr 100 105 110 Val Gly Phe Thr Asp Ser Arg Lys Ile Ser His Thr Cys Thr His Pro 115 120 125 Phe His His Glu Pro Pro Val Ile Gly Arg Glu Arg Phe His Ser Arg 130 135 140 Pro Gln His Gly Lys Glu Leu Pro Cys Ser Thr Tyr Val Gln Ser Thr 145 150 155 160 Ala Ala Thr Ala Glu Glu Ile Glu Val His Met Pro Pro Asp Thr Pro 165 170 175 Asp Arg Thr Leu Met Thr Gln Gln Ser Gly Asn Val Lys Ile Thr Val 180 185 190 Asn Gly Gln Thr Val Arg Tyr Lys Cys Asn Cys Gly Gly Ser Gly Gly 195 200 205 Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala 210 215 220 Asn Pro Asn Ala Asn Pro Asn Ala Gly Gly Ser Asn Glu Gly Leu Thr 225 230 235 240 Thr Thr Asp Lys Val Ile Asn Asn Cys Lys Ile Asp Gln Cys His Ala 245 250 255 Ala Val Thr Asn His Lys Asn Trp Gln Tyr Asn Ser Pro Leu Val Pro 260 265 270 Arg Asn Ala Glu Leu Gly Asp Arg Lys Gly Lys Ile His Ile Pro Phe 275 280 285 Pro Leu Ala Asn Val Thr Cys Arg Val Pro Lys Ala Arg Asn Pro Thr 290 295 300 Val Thr Tyr Gly Lys Asn Gln Val Thr Met Leu Leu Tyr Pro Asp His 305 310 315 320 Pro Thr Leu Leu Ser Tyr Arg Asn Met Gly Gln Glu Pro Asn Tyr His 325 330 335 Glu Glu Trp Val Thr His Lys Lys Glu Val Thr Leu Thr Val Pro Thr 340 345 350 Glu Gly Leu Glu Val Thr Trp Gly Asn Asn Glu Pro Tyr Lys Tyr Trp 355 360 365 Pro Gln Met Ser Thr Asn Gly Thr Ala His Gly His Pro His Glu Ile 370 375 380 Ile Leu Tyr Tyr Tyr Glu Leu Tyr Pro Thr Met Thr Val Val Ile Val 385 390 395 400 Ser Val Ala Ser Phe Val Leu Leu Ser Met Val Gly Thr Ala Val Gly 405 410 415 Met Cys Val Cys Ala Arg Arg Arg Cys Ile Thr Pro Tyr Glu Leu Thr 420 425 430 Pro Gly Ala Thr Val Pro Phe Leu Leu Ser Leu Leu Cys Cys Val Arg 435 440 445 Thr Thr Lys Ala 450 <210> 51 <211> 439 <212> PRT <213> Artificial <220> <223> CHIKV E1 <400> 51 Tyr Glu His Val Thr Val Ile Pro Asn Thr Val Gly Val Pro Tyr Lys 1 5 10 15 Thr Leu Val Asn Arg Pro Gly Tyr Ser Pro Met Val Leu Glu Met Glu 20 25 30 Leu Gln Ser Val Thr Leu Glu Pro Thr Leu Ser Leu Asp Tyr Ile Thr 35 40 45 Cys Glu Tyr Lys Thr Val Ile Pro Ser Pro Tyr Val Lys Cys Cys Gly 50 55 60 Thr Ala Glu Cys Lys Asp Lys Ser Leu Pro Asp Tyr Ser Cys Lys Val 65 70 75 80 Phe Thr Gly Val Tyr Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe Cys 85 90 95 Asp Ala Glu Asn Thr Gln Leu Ser Glu Ala His Val Glu Lys Ser Glu 100 105 110 Ser Cys Lys Thr Glu Phe Ala Ser Ala Tyr Arg Ala His Thr Ala Ser 115 120 125 Ala Ser Ala Lys Leu Arg Val Leu Tyr Gln Gly Asn Asn Ile Thr Val 130 135 140 Ala Ala Tyr Ala Asn Gly Asp His Ala Val Thr Val Lys Asp Ala Lys 145 150 155 160 Phe Val Val Gly Pro Met Ser Ser Ala Trp Thr Pro Phe Asp Asn Lys 165 170 175 Ile Val Val Tyr Lys Gly Asp Val Tyr Asn Met Asp Tyr Pro Pro Phe 180 185 190 Gly Ala Gly Arg Pro Gly Gln Phe Gly Asp Ile Gln Ser Arg Thr Pro 195 200 205 Glu Ser Lys Asp Val Tyr Ala Asn Thr Gln Leu Val Leu Gln Arg Pro 210 215 220 Ala Ala Gly Thr Val His Val Pro Tyr Ser Gln Ala Pro Ser Gly Phe 225 230 235 240 Lys Tyr Trp Leu Lys Glu Arg Gly Ala Ser Leu Gln His Thr Ala Pro 245 250 255 Phe Gly Cys Gln Ile Ala Thr Asn Pro Val Arg Ala Val Asn Cys Ala 260 265 270 Val Gly Asn Ile Pro Ile Ser Ile Asp Ile Pro Asp Ala Ala Phe Thr 275 280 285 Arg Val Val Asp Ala Pro Ser Val Thr Asp Met Ser Cys Glu Val Pro 290 295 300 Ala Cys Thr His Ser Ser Asp Phe Gly Gly Val Ala Ile Ile Lys Tyr 305 310 315 320 Thr Ala Ser Lys Lys Gly Lys Cys Ala Val His Ser Met Thr Asn Ala 325 330 335 Val Thr Ile Arg Glu Ala Asp Val Glu Val Glu Gly Asn Ser Gln Leu 340 345 350 Gln Ile Ser Phe Ser Thr Ala Leu Ala Ser Ala Glu Phe Arg Val Gln 355 360 365 Val Cys Ser Thr Gln Val His Cys Ala Ala Ala Cys His Pro Pro Lys 370 375 380 Asp His Ile Val Asn Tyr Pro Ala Ser His Thr Thr Leu Gly Val Gln 385 390 395 400 Asp Ile Ser Thr Thr Ala Met Ser Trp Val Gln Lys Ile Thr Gly Gly 405 410 415 Val Gly Leu Ile Val Ala Val Ala Ala Leu Ile Leu Ile Val Val Leu 420 425 430 Cys Val Ser Phe Ser Arg His 435 <210> 52 <211> 261 <212> PRT <213> Artificial <220> <223> CHIKV capsid <400> 52 Met Glu Phe Ile Pro Thr Gln Thr Phe Tyr Asn Arg Arg Tyr Gln Pro 1 5 10 15 Arg Pro Trp Ala Pro Arg Pro Thr Ile Gln Val Ile Arg Pro Arg Pro 20 25 30 Arg Pro Gln Arg Gln Ala Gly Gln Leu Ala Gln Leu Ile Ser Ala Val 35 40 45 Asn Lys Leu Thr Met Arg Ala Val Pro Gln Gln Lys Pro Arg Arg Asn 50 55 60 Arg Lys Asn Lys Lys Gln Arg Gln Lys Lys Gln Ala Pro Gln Asn Asp 65 70 75 80 Pro Lys Gln Lys Lys Gln Pro Pro Gln Lys Lys Pro Ala Gln Lys Lys 85 90 95 Lys Lys Pro Gly Arg Arg Glu Arg Met Cys Met Lys Ile Glu Asn Asp 100 105 110 Cys Ile Phe Glu Val Lys His Glu Gly Lys Val Met Gly Tyr Ala Cys 115 120 125 Leu Val Gly Asp Lys Val Met Lys Pro Ala His Val Lys Gly Thr Ile 130 135 140 Asp Asn Ala Asp Leu Ala Lys Leu Ala Phe Lys Arg Ser Ser Lys Tyr 145 150 155 160 Asp Leu Glu Cys Ala Gln Ile Pro Val His Met Lys Ser Asp Ala Ser 165 170 175 Lys Phe Thr His Glu Lys Pro Glu Gly Tyr Tyr Asn Trp His His Gly 180 185 190 Ala Val Gln Tyr Ser Gly Gly Arg Phe Thr Ile Pro Thr Gly Ala Gly 195 200 205 Lys Pro Gly Asp Ser Gly Arg Pro Ile Phe Asp Asn Lys Gly Arg Val 210 215 220 Val Ala Ile Val Leu Gly Gly Ala Asn Glu Gly Ala Arg Thr Ala Leu 225 230 235 240 Ser Val Val Thr Trp Asn Lys Asp Ile Val Thr Lys Ile Thr Pro Glu 245 250 255 Gly Ala Glu Glu Trp 260 <210> 53 <211> 453 <212> PRT <213> Artificial <220> <223> VEEV E2-74 fusion protein <400> 53 Ser Thr Glu Glu Leu Phe Asn Glu Tyr Lys Leu Thr Arg Pro Tyr Met 1 5 10 15 Ala Arg Cys Ile Arg Cys Ala Val Gly Ser Cys His Ser Pro Ile Ala 20 25 30 Ile Glu Ala Val Lys Ser Asp Gly His Asp Gly Tyr Val Arg Leu Gln 35 40 45 Thr Ser Ser Gln Tyr Gly Leu Asp Ser Ser Gly Asn Leu Lys Gly Arg 50 55 60 Thr Met Arg Tyr Asp Met His Gly Thr Ile Lys Glu Ile Pro Leu His 65 70 75 80 Gln Val Ser Leu Tyr Thr Ser Arg Pro Cys His Ile Val Asp Gly His 85 90 95 Gly Tyr Phe Leu Leu Ala Arg Cys Pro Ala Gly Asp Ser Ile Thr Met 100 105 110 Glu Phe Lys Lys Asp Ser Val Arg His Ser Cys Ser Val Pro Tyr Glu 115 120 125 Val Lys Phe Asn Pro Val Gly Arg Glu Leu Tyr Thr His Pro Pro Glu 130 135 140 His Gly Val Glu Gln Ala Cys Gln Val Tyr Ala His Asp Ala Gln Asn 145 150 155 160 Arg Gly Ala Tyr Val Glu Met His Leu Pro Gly Ser Glu Val Asp Ser 165 170 175 Ser Leu Val Ser Leu Ser Gly Ser Ser Gly Gly Asn Pro Asn Ala Asn 180 185 190 Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn 195 200 205 Pro Asn Ala Gly Gly Ser Ser Val Thr Val Thr Pro Pro Asp Gly Thr 210 215 220 Ser Ala Leu Val Glu Cys Glu Cys Gly Gly Thr Lys Ile Ser Glu Thr 225 230 235 240 Ile Asn Lys Thr Lys Gln Phe Ser Gln Cys Thr Lys Lys Glu Gln Cys 245 250 255 Arg Ala Tyr Arg Leu Gln Asn Asp Lys Trp Val Tyr Asn Ser Asp Lys 260 265 270 Leu Pro Lys Ala Ala Gly Ala Thr Leu Lys Gly Lys Leu His Val Pro 275 280 285 Phe Leu Leu Ala Asp Gly Lys Cys Thr Val Pro Leu Ala Pro Glu Pro 290 295 300 Met Ile Thr Phe Gly Phe Arg Ser Val Ser Leu Lys Leu His Pro Lys 305 310 315 320 Asn Pro Thr Tyr Leu Ile Thr Arg Gln Leu Ala Asp Glu Pro His Tyr 325 330 335 Thr His Glu Leu Ile Ser Glu Pro Ala Val Arg Asn Phe Thr Val Thr 340 345 350 Glu Lys Gly Trp Glu Phe Val Trp Gly Asn His Pro Pro Lys Arg Phe 355 360 365 Trp Ala Gln Glu Thr Ala Pro Gly Asn Pro His Gly Leu Pro His Glu 370 375 380 Val Ile Thr His Tyr Tyr His Arg Tyr Pro Met Ser Thr Ile Leu Gly 385 390 395 400 Leu Ser Ile Cys Ala Ala Ile Ala Thr Val Ser Val Ala Ala Ser Thr 405 410 415 Trp Leu Phe Cys Arg Ser Arg Val Ala Cys Leu Thr Pro Tyr Arg Leu 420 425 430 Thr Pro Asn Ala Arg Ile Pro Phe Cys Leu Ala Val Leu Cys Cys Ala 435 440 445 Arg Thr Ala Arg Ala 450 <210> 54 <211> 442 <212> PRT <213> Artificial <220> <223> VEEV E1 <400> 54 Tyr Glu His Ala Thr Thr Met Pro Ser Gln Ala Gly Ile Ser Tyr Asn 1 5 10 15 Thr Ile Val Asn Arg Ala Gly Tyr Ala Pro Leu Pro Ile Ser Ile Thr 20 25 30 Pro Thr Lys Ile Lys Leu Ile Pro Thr Val Asn Leu Glu Tyr Val Thr 35 40 45 Cys His Tyr Lys Thr Gly Met Asp Ser Pro Ala Ile Lys Cys Cys Gly 50 55 60 Ser Gln Glu Cys Thr Pro Thr Tyr Arg Pro Asp Glu Gln Cys Lys Val 65 70 75 80 Phe Thr Gly Val Tyr Pro Phe Met Trp Gly Gly Ala Tyr Cys Phe Cys 85 90 95 Asp Thr Glu Asn Thr Gln Val Ser Lys Ala Tyr Val Met Lys Ser Asp 100 105 110 Asp Cys Leu Ala Asp His Ala Glu Ala Tyr Lys Ala His Thr Ala Ser 115 120 125 Val Gln Ala Phe Leu Asn Ile Thr Val Gly Glu His Ser Ile Val Thr 130 135 140 Thr Val Tyr Val Asn Gly Glu Thr Pro Val Asn Phe Asn Gly Val Lys 145 150 155 160 Ile Thr Ala Gly Pro Leu Ser Thr Ala Trp Thr Pro Phe Asp Arg Lys 165 170 175 Ile Val Gln Tyr Ala Gly Glu Ile Tyr Asn Tyr Asp Phe Pro Glu Tyr 180 185 190 Gly Ala Gly Gln Pro Gly Ala Phe Gly Asp Ile Gln Ser Arg Thr Val 195 200 205 Ser Ser Ser Asp Leu Tyr Ala Asn Thr Asn Leu Val Leu Gln Arg Pro 210 215 220 Lys Ala Gly Ala Ile His Val Pro Tyr Thr Gln Ala Pro Ser Gly Phe 225 230 235 240 Glu Gln Trp Lys Lys Asp Lys Ala Pro Ser Leu Lys Phe Thr Ala Pro 245 250 255 Phe Gly Cys Glu Ile Tyr Thr Asn Pro Ile Arg Ala Glu Asn Cys Ala 260 265 270 Val Gly Ser Ile Pro Leu Ala Phe Asp Ile Pro Asp Ala Leu Phe Thr 275 280 285 Arg Val Ser Glu Thr Pro Thr Leu Ser Ala Ala Glu Cys Thr Leu Asn 290 295 300 Glu Cys Val Tyr Ser Ser Asp Phe Gly Gly Ile Ala Thr Val Lys Tyr 305 310 315 320 Ser Ala Ser Lys Ser Gly Lys Cys Ala Val His Val Pro Ser Gly Thr 325 330 335 Ala Thr Leu Lys Glu Ala Ala Val Glu Leu Thr Glu Gln Gly Ser Ala 340 345 350 Thr Ile His Phe Ser Thr Ala Asn Ile His Pro Glu Phe Arg Leu Gln 355 360 365 Ile Cys Thr Ser Tyr Val Thr Cys Lys Gly Asp Cys His Pro Pro Lys 370 375 380 Asp His Ile Val Thr His Pro Gln Tyr His Ala Gln Thr Phe Thr Ala 385 390 395 400 Ala Val Ser Lys Thr Ala Trp Thr Trp Leu Thr Ser Leu Leu Gly Gly 405 410 415 Ser Ala Val Ile Ile Ile Ile Gly Leu Val Leu Ala Thr Ile Val Ala 420 425 430 Met Tyr Val Leu Thr Asn Gln Lys His Asn 435 440 <210> 55 <211> 275 <212> PRT <213> Artificial <220> <223> VEEV Capsid <400> 55 Met Phe Pro Phe Gln Pro Met Tyr Pro Met Gln Pro Met Pro Tyr Arg 1 5 10 15 Asn Pro Phe Ala Ala Pro Arg Arg Pro Trp Phe Pro Arg Thr Asp Pro 20 25 30 Phe Leu Ala Met Gln Val Gln Glu Leu Thr Arg Ser Met Ala Asn Leu 35 40 45 Thr Phe Lys Gln Arg Arg Asp Ala Pro Pro Glu Gly Pro Ser Ala Asn 50 55 60 Lys Pro Lys Lys Glu Ala Ser Gln Lys Gln Lys Gly Gly Gly Gln Gly 65 70 75 80 Lys Lys Lys Lys Asn Gln Gly Lys Lys Lys Ala Lys Thr Gly Pro Pro 85 90 95 Asn Pro Lys Ala Gln Asn Gly Asn Lys Lys Lys Thr Asn Lys Lys Pro 100 105 110 Gly Lys Arg Gln Arg Met Val Met Lys Leu Glu Ser Asp Lys Thr Phe 115 120 125 Pro Ile Met Leu Glu Gly Lys Ile Asn Gly Tyr Ala Cys Val Val Gly 130 135 140 Gly Lys Leu Phe Arg Pro Met His Val Glu Gly Lys Ile Asp Asn Asp 145 150 155 160 Val Leu Ala Ala Leu Lys Thr Lys Lys Ala Ser Lys Tyr Asp Leu Glu 165 170 175 Tyr Ala Asp Val Pro Gln Asn Met Arg Ala Asp Thr Phe Lys Tyr Thr 180 185 190 His Glu Lys Pro Gln Gly Tyr Tyr Ser Trp His His Gly Ala Val Gln 195 200 205 Tyr Glu Asn Gly Arg Phe Thr Val Pro Lys Gly Val Gly Ala Lys Gly 210 215 220 Asp Ser Gly Arg Pro Ile Leu Asp Asn Gln Gly Arg Val Val Ala Ile 225 230 235 240 Val Leu Gly Gly Val Asn Glu Gly Ser Arg Thr Ala Leu Ser Val Val 245 250 255 Met Trp Asn Glu Lys Gly Val Thr Val Lys Tyr Thr Pro Glu Asn Cys 260 265 270 Glu Gln Trp 275 <210> 56 <211> 414 <212> PRT <213> Plasmodium falciparum <400> 56 Met Met Arg Lys Leu Ala Ile Leu Ser Val Ser Ser Phe Leu Phe Val 1 5 10 15 Glu Ala Leu Phe Gln Glu Tyr Gln Cys Tyr Gly Ser Ser Ser Asn Thr 20 25 30 Arg Val Leu Asn Glu Leu Asn Tyr Asp Asn Ala Gly Thr Asn Leu Tyr 35 40 45 Asn Glu Leu Glu Met Asn Tyr Tyr Gly Lys Gln Glu Asn Trp Tyr Ser 50 55 60 Leu Lys Lys Asn Ser Arg Ser Leu Gly Glu Asn Asp Asp Gly Asn Asn 65 70 75 80 Asn Asn Gly Asp Asn Gly Arg Glu Gly Lys Asp Glu Asp Lys Arg Asp 85 90 95 Gly Asn Asn Glu Asp Asn Glu Lys Leu Arg Lys Pro Lys His Lys Lys 100 105 110 Leu Lys Gln Pro Gly Asp Gly Asn Pro Asp Pro Asn Ala Asn Pro Asn 115 120 125 Val Asp Pro Asn Ala Asn Pro Asn Val Asp Pro Asn Ala Asn Pro Asn 130 135 140 Val Asp Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 145 150 155 160 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 165 170 175 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 180 185 190 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 195 200 205 Val Asp Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 210 215 220 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 225 230 235 240 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 245 250 255 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 260 265 270 Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn 275 280 285 Lys Asn Asn Gln Gly Asn Gly Gln Gly His Asn Met Pro Asn Asp Pro 290 295 300 Asn Arg Asn Val Asp Glu Asn Ala Asn Ala Asn Asn Ala Val Lys Asn 305 310 315 320 Asn Asn Asn Glu Glu Pro Ser Asp Lys His Ile Glu Gln Tyr Leu Lys 325 330 335 Lys Ile Lys Asn Ser Ile Ser Thr Glu Trp Ser Pro Cys Ser Val Thr 340 345 350 Cys Gly Asn Gly Ile Gln Val Arg Ile Lys Pro Gly Ser Ala Asn Lys 355 360 365 Pro Lys Asp Glu Leu Asp Tyr Glu Asn Asp Ile Glu Lys Lys Ile Cys 370 375 380 Lys Met Glu Lys Cys Ser Ser Val Phe Asn Val Val Asn Ser Ser Ile 385 390 395 400 Gly Leu Ile Met Val Leu Ser Phe Leu Phe Leu Asn Thr Arg 405 410 1 / 304

Claims (17)

  1. 치쿤군야 바이러스 (CHIKV) 또는 베네수엘라 말뇌염 바이러스 (VEEV) 바이러스-유사 입자로서,
    상기 바이러스-유사 입자는 융합 단백질을 형성하기 위해 E2 외피 단백질에 삽입되는 하나 이상의 말라리아 항원을 포함하고,
    상기 하나 이상의 말라리아 항원은 SEQ ID NO:1 또는 2 의 잔기 509-512 사이의 부위, 잔기 519-520 사이의 부위, 잔기 529-530 사이의 부위, 또는 잔기 531-532 사이의 부위에 상응하는 부위에서 CHIKV E2 외피 단백질 내에 삽입되거나; 또는 상기 하나 이상의 말라리아 항원은 SEQ ID NO:3 의 잔기 515-520 사이의 부위, 또는 잔기 536-539 사이의 부위에 상응하는 부위에서 VEEV E2 외피 단백질 내에 삽입되고,
    상기 하나 이상의 말라리아 항원은 (a) 및 (b) 로 이루어진 군으로부터 선택되는 것인, 바이러스-유사 입자:
    (a) (NPNA)n, 여기서, n 은 4 내지 30 임; 및
    (b) (EYLNKIQNSLSTEWSPCSVT)y, 여기서, y 는 1 내지 6 임.
  2. 제 1 항에 있어서, 캡시드, 외피 단백질 E1 및 E2 를 포함하는 바이러스-유사 입자.
  3. 제 1 항에 있어서, 바이러스-유사 입자가 외피 단백질 E1, E2 및 캡시드 단백질을 포함하고,
    상기 외피 단백질 E2 가 SEQ ID No.50 의 아미노산 서열로 이루어지고;
    상기 외피 단백질 E1 이 SEQ ID No.51 의 아미노산 서열로 이루어지고;
    상기 캡시드 단백질이 SEQ ID No.52 의 아미노산 서열로 이루어지는 바이러스-유사 입자.
  4. 제 1 항에 있어서, 입자가 항원이 그 안에 삽입되는 외피 단백질 E2 1 종 이상, 외피 단백질 E1 1 종 이상 및 캡시드 1 종 이상으로 이루어진 베네수엘라 말뇌염 바이러스 유사 입자이고,
    항원이 그 안에 삽입되는 외피 단백질 E2 가 SEQ ID NO.53 으로 표시되는 아미노산 서열로 이루어지고; 외피 단백질 E1 이 SEQ ID NO.54 로 표시되는 아미노산 서열로 이루어지고; 캡시드가 SEQ ID NO.55 로 표시되는 아미노산 서열로 이루어지는 바이러스-유사 입자.
  5. 제 1 항에 따른 입자의 발현을 위한 뉴클레오티드를 포함하는 단리된 핵산 분자.
  6. SEQ ID No. 26-27, 29-30, 32-33, 35-36, 38, 40 또는 42 으로 표시되는 뉴클레오티드 서열로 이루어진 단리된 핵산 분자.
  7. 제 5 항에 따른 핵산 분자를 포함하는 벡터로서, 핵산 분자에 작동가능하게 연결된 발현 조절 서열을 포함하거나 또는 포함하지 않는 벡터.
  8. (a) 제 1 항에 따른 입자 및/또는 제 1 항에 따른 입자의 발현을 위한 뉴클레오티드 서열을 포함하는 핵산 분자; 및
    (b) 약학적으로 허용가능한 담체
    를 포함하는 말라리아의 예방 또는 치료를 위한 약학적 조성물.
  9. 제 1 항에 따른 바이러스-유사 입자를 포함하는 백신 조성물.
  10. 제 8 항에 따른 조성물의 유효량을 인간을 제외한 포유류에게 투여하는 것을 포함하는 말라리아 치료 방법.
  11. 개별적인 성분으로, 하나 이상의 제 1 말라리아 항원 또는 하나 이상의 제 1 말라리아 항원을 인코딩하는 하나 이상의 폴리뉴클레오티드를 포함하는 프라이밍 조성물; 및 하나 이상의 제 2 말라리아 항원 또는 하나 이상의 제 2 말라리아 항원을 인코딩하는 하나 이상의 폴리뉴클레오티드를 포함하는 하나 이상의 폴리펩티드를 포함하는 부스팅 조성물을 포함하는 백신으로서, 상기 조성물 중 하나 이상은 제 1 항에 따른 바이러스-유사 입자, 또는 상기 바이러스-유사 입자를 인코딩하는 핵산을 포함하는 백신.
  12. 제 11 항에 있어서, 폴리뉴클레오티드가 모든 포자소체 단백질을 인코딩하는, 백신.
  13. 제 9 항에 있어서, 말라리아의 예방 또는 치료에 사용하기 위한 백신 조성물.
  14. (a) 제 1 항에 따른 바이러스-유사 입자를 포함하는 제 1 백신 조성물; 및
    (b) 제 1 항에 따른 바이러스-유사 입자를 포함하는 제 2 백신 조성물
    을 포함하는 키트로서,
    제 1 백신 조성물에 함유된 바이러스-유사 입자는 제 2 백신 조성물에 함유된 바이러스-유사 입자와 상이한 바이러스-유사 입자인 키트.
  15. 제 14 항에 있어서, 추가로 (c) 제 1 항에 따른 바이러스-유사 입자를 포함하는 제 3 백신 조성물을 포함하는 키트로서, 제 1 백신 조성물이 면역화의 프라이밍에 사용되고, 제 2 및 제 3 백신 조성물이 면역화의 부스팅에 사용되며, 제 3 백신 조성물에 함유된 바이러스-유사 입자가 제 1 및 및 제 2 백신 조성물에 함유된 바이러스-유사 입자와 상이하거나, 또는 제 1 또는 제 2 백신 조성물에 함유된 입자와 동일한 키트.
  16. 제 1 항에 있어서, 1 또는 2 개의 링커가 하나 이상의 말라리아 항원의 N-말단 잔기와 상기 E2 외피 단백질 사이 및/또는 하나 이상의 말라리아 항원의 C-말단 잔기와 상기 E2 외피 단백질 사이에 개재되는 바이러스-유사 입자.
  17. 제 1 항에 있어서, 바이러스-유사 입자가 SEQ ID NO.: 28, 31, 39 및 41 로 이루어진 군에서 선택되는 아미노산 서열을 포함하는 바이러스-유사 입자.
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