Abstract
A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.
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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AIDS Vaccines / immunology*
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Amino Acid Sequence
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Animals
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Antibodies, Neutralizing / immunology
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Disease Susceptibility / immunology
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Female
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Founder Effect
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HIV Antibodies / immunology
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HIV Infections / immunology
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HIV Infections / prevention & control*
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HIV Infections / virology*
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HIV-1 / chemistry
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HIV-1 / immunology*
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Humans
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Immune Evasion / immunology
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Macaca mulatta
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Male
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Molecular Sequence Data
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Phylogeny
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Risk
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SAIDS Vaccines / immunology*
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Simian Acquired Immunodeficiency Syndrome / immunology
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Simian Acquired Immunodeficiency Syndrome / prevention & control
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Simian Acquired Immunodeficiency Syndrome / virology
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Simian Immunodeficiency Virus / chemistry
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Simian Immunodeficiency Virus / genetics
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Simian Immunodeficiency Virus / immunology*
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Simian Immunodeficiency Virus / physiology
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env Gene Products, Human Immunodeficiency Virus / immunology
Substances
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AIDS Vaccines
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Antibodies, Neutralizing
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HIV Antibodies
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SAIDS Vaccines
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env Gene Products, Human Immunodeficiency Virus