Abstract
Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins. Here we demonstrate that a single low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope glycoproteins of a strain from the ZIKV outbreak in 2013 elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNP protected mice against ZIKV challenges at 2 weeks or 5 months after vaccination, and a single dose of 50 μg was sufficient to protect non-human primates against a challenge at 5 weeks after vaccination. These data demonstrate that nucleoside-modified mRNA-LNP elicits rapid and durable protective immunity and therefore represents a new and promising vaccine candidate for the global fight against ZIKV.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Neutralizing / immunology
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Antibodies, Viral / immunology
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Antigens, Viral / genetics
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Antigens, Viral / immunology
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Female
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Glycoproteins / genetics
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Glycoproteins / immunology
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Injections, Intradermal
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Macaca mulatta / immunology
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Macaca mulatta / virology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Nanoparticles / administration & dosage
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Nanoparticles / chemistry
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RNA Stability
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RNA, Messenger / administration & dosage*
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RNA, Messenger / chemistry*
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RNA, Messenger / genetics
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RNA, Viral / administration & dosage
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RNA, Viral / chemistry
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RNA, Viral / genetics
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Time Factors
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Vaccination
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / immunology
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Viral Vaccines / administration & dosage
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Viral Vaccines / immunology*
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Zika Virus / chemistry
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Zika Virus / genetics
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Zika Virus / immunology*
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Zika Virus Infection / immunology
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Zika Virus Infection / prevention & control*
Substances
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Antibodies, Neutralizing
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Antibodies, Viral
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Antigens, Viral
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Glycoproteins
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RNA, Messenger
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RNA, Viral
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Viral Envelope Proteins
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Viral Vaccines