Abstract
How well antibodies can protect against disease due to HIV-1 infection remains a pivotal but unresolved issue with important implications for vaccine design and the use of prophylactic antibody to prevent infection after accidental exposure to the virus and to interrupt transmission of virus from mother to child. Strong doubts about the possible utility of antibodies in vivo have been raised because of the relative resistance of primary viruses to antibody neutralization in vitro. Primary viruses are likely to be close to the viruses transmitted during natural infection in humans. Vaccine studies have been of little value in assessing antibody efficacy in vivo because none of the strategies described to date have elicited significant neutralizing antibody responses to primary viruses (reviewed in ref. 1). Passive immunization studies are similarly hindered by the paucity of reagents able to neutralize primary viruses effectively2 and a single study has suggested some benefit3. Here we describe experiments to explore the ability of passive antibody to protect against primary virus challenge in hu-PBL-SCID mice. In this model, severe combined immunodeficient (SCID) mice are populated with human peripheral blood mononuclear celI (PBMCs) and infected with HIV-1 (ref. 4). We find that the potent neutralizing human monoclonal antibody lgG1b12 at high dose is able to completely protect even when given several hours after viral challenge. The results are encouraging for antibody-based postexposure prophylaxis and support the notion that antibody induction could contribute to an effective vaccine.
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Haynes, B.F. HIV vaccines: Where we are and where we are going. Lancet 348, 933–937 (1996).
Burton, D.R. & Montefiori, D.C. The antibody response in HIV-1 infection. AIDS 11 (Suppl. A), S87–S98 (1997).
Conley, A.J. et al. The consequence of passive administration of an anti-human immunodeficiency virus type 1 neutralizing monoclonal antibody before challenge of chimpanzees with a primary virus isolate. J. Virol. 70, 6751–6758 (1996).
Mosier, D.E. et al. Human immunodeficiency virus infection of human-PBL-SCID mice. Science 251, 791–794 (1991).
Girard, M., Barré-Sinoussi, F., van der Ryst L. & Fultz P. Vaccination of chimpanzees against HIV-1. Antibiot. Chemother. 48, 121–124 (1996).
Emini, E.A. et al. Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. Nature 355, 728–730 (1992).
Cohen, J. et al. Jitters jeopardize AIDS vaccine trials. Science 262, 980–981 (1993).
Mascola, J.R. et al. Two antigenically distinct subtypes of human immunodeficiency virus type 1: Viral genotype predicts neutralization serotype. J. Infect. Dis. 169, 48–54 (1994).
Matthews, T.J. Dilemma of neutralization resistance of HIV-1 field isolates and vaccine development. AIDS Res. Hum. Retroviruses 10, 631–632 (1994).
Moore, J.P. & Ho, D.D. HIV-1 neutralization: The consequences of viral adaptation to growth on transformed T cells. AIDS 9 (Suppl. A), 5117–5136 (1995).
Koup, R.A., Safrit J.T., Weir, R. & Gauduin M.C. Defining antibody protection against HIV-1 transmission in HU-PBL-SCID mice. Semin. Immunol. 8, 263–268 (1996).
Safrit, J.T. et al. Hu-PBL-SCID mice can be protected from HIV-1 infection by passive transfer of monoclonal antibody to the principal neutralizing determinant of envelope gp120. AIDS 7, 15–21 (1993).
Gauduin, M.C., Safrit, J.T., Weir, R., Fung, M.S. & Koup, R.A. Pre-and post exposure protection against human immunodeficiency virus type 1 infection mediated by a monoclonal antibody. J Infect. Dis. 171, 1203–1209 (1995).
Parren, P.W.H.I. et al. Protection against HIV-1 infection in hu-PBL-SCID mice by passive immunization with a neutralizing human monoclonal antibody against the gp120 CD4-binding site. AIDS 9, F1–F6 (1995).
Burton, D.R. et al. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science 266, 1024–1027 (1994).
Gauduin, M.C. et al. Effective ex vivo neutralization of human immunodeficiency virus type 1 in plasma HIV-1 by recombinant immunoglobuliH molecules. J. Virol. 70, 2586–2592 (1996).
Zuckier, L.S., Rodriguez, L.D. & Scharff, M.D. Immunologic and pharmacologic concepts of monoclonal antibodies. Seminars in Nuclear Medicine 19, 166–186 (1989).
Trkola, A. et al. Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-lgG. J. Virol. 69, 6609–6617 (1995).
Koyanagi, Y. et al. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science 236, 819–822 (1987).
Koup, R.A. et al. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J. Virol. 68, 4650–4655 (1994).
White-Scharf, M.E. et al. Broadly neutralizing monoclonal antibodies to the V3 region of HIV-1 can be elicited by peptide immunization. Virol. 192, 197–206 (1993).
Prince, A.M. et al. Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV. Proc. Natl. Acad. Sci. USA 85, 6944–6948 (1988).
Lambert, J.S. et al. Safety and pharmacokinetics of hyperimmune anti-human immunodeficiency virus (HIV) immunoglobulin administered to HIV-infected pregnant women and their newborns. J. Infect. Dis. 175, 283–291 (1997).
Cummins, L.M. et al. Preparation and characterization of an intravenous solution of IgG from human immunodeficiency virus-seropositive donors. Blood 77, 1111–1117 (1991).
Trkola, A. et al. CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature 384, 184–187 (1996).
Klasse, P.J. & Moore, J.P. Quantitative model of antibody-and soluble CD4-mediated neutralization of primary isolates and T-cell line-adapted strains of human immunodeficiency virus type 1. J. Virol. 70, 3668–3677 (1996).
Wei, X. et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373, 117–122 (1995).
Ho, D.D. et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373, 123–126 (1995).
Perelson, A.S., Neumann, A.U., Markowitz, M., Leonard, J.M. & Ho, D.D. HIV-1 dynamics in vivo: Virion clearance rate, infected cell life-span, and viral generation time. Science 271, 1582–1586 (1996).
Zolla-Pazner, S. & Sharpe, S.A. A resting cell assay for improved detection of antibody-mediated neutralization of HIV type 1 primary isolates. AIDS Res. Hum. Retroviruses 11, 1449–1457 (1995).
Burton, D.R. A vaccine for HIV type 1: The antibody perspective. Proc. Natl. Acad. Sci. USA 94, 10018–10023 (1997).
Kessler, J.A. et al. The recombinant human monoclonal antibody IgG1b12 neutralizes diverse human immunodeficiency virus type 1 primary isolates. AIDS Res. Hum. Retroviruses 13, 575–582 (1997).
Burton, D.R. et al. A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc. Natl. Acad. Sci. USA 88, 10134–10137 (1991).
Roben, P. et al. Recognition properties of a panel of human recombinant Fab fragments to the CD4 binding site of gp120 that show differing abilities to neutralize human immunodeficiency virus type 1. J. Virol. 68, 4821–4828 (1994).
D'Souza, M.P. et al. Evaluation of monoclonal antibodies to HIV-1 primary isolates by neutralization assays: Performance criteria for selecting candidate antibodies for clinical trials. J. Infect. Dis. 175, 1056–1062 (1997).
Allaway, G.P. et al. Expression and characterization of CD4-lgG2, a novel heterotetramer that neutralizes primary HIV type 1 isolates. AIDS Res. Hum. Retroviruses 11, 533–539 (1995).
Mosier, D.E., Gulizia, R.J., Baird, S.M. & Wilson, D.B. Transfer of functional human immune system in mice with severe combined immunodeficiency. Nature 355, 728–730 (1988).
Hesselton, R.M. et al. Human peripheral blood xenografts in the SCID mouse: Characterization of immunologic reconstitution. J. Infect. Dis. 168, 630–640 (1993).
Ho, D.D., Moudgil, T. & Alam, M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N. Engl. J. Med. 321, 1621–1625 (1989).
Koup, R.A. & Ho, D.D. Quantitative culture assay for HIV-1 in peripheral blood. in Techniques in HIV Research (eds. Aldovini, A. & Walker, B.D.) 107–112 (Stockton, New York, 1994).
Barré-Sinoussi, F. et al. Isolation of a T-lymphocyte retrovirus from patient at risk for acquired immunodeficiency syndrome (AIDS). Science 220, 868–871 (1983).
Moore, J.P., Cao, Y., Ho, D.D. & Koup, R.A. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J. Virol. 68, 5142–5155 (1994).
Ho, D.D. et al. Another discontinuous epitope on glycoprotein gp l20 that is important in human immunodeficiency virus type 1 neutralization is identified by a monoclonal antibody. Proc. Natl. Acad. Sci. USA 88, 8949–8952 (1991).
Ho, D.D. et al. Conformational epitope on gp120 important in CD4 binding and human immunodeficiency virus type 1 neutralization identified by a human monoclonal antibody. J. Virol. 65, 489–93 (1991).
Ho, D.D. et al. Human immunodeficiency virus neutralizing antibodies recognize several conserved domains on the envelope glycoproteins. J. Virol. 61, 2024–2028 (1987).
Koup, R.A., Hesselton, R.M., Safrit, J.T., Somasundran, M. & Sullivan, J.L. Quantitative assessment of human immunodeficiency virus type 1 replication in human xenografts of acute-infected Hu-PBL-SCID mice. AIDS Res. Hum. Retroviruses 10, 279–284 (1994).
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Gauduin, MC., Parren, P., Weir, R. et al. Passive immunization with a human monoclonal antibody protects hu-PBL-SCID mice against challenge by primary isolates of HIV-1. Nat Med 3, 1389–1393 (1997). https://doi.org/10.1038/nm1297-1389
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DOI: https://doi.org/10.1038/nm1297-1389
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