Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV

Mario Roederer, Brandon F. Keele, Stephen D. Schmidt, Rosemarie D. Mason, Hugh C. Welles, Will Fischer, Celia Labranche, Kathryn E. Foulds, Mark K. Louder, Zhi Yong Yang, John Paul M. Todd, Adam P. Buzby, Linh V. Mach, Ling Shen, Kelly E. Seaton, Brandy M. Ward, Robert T. Bailer, Raphael Gottardo, Wenjuan Gu, Guido FerrariS. Munir Alam, Thomas N. Denny, David C. Montefiori, Georgia D. Tomaras, Bette T. Korber, Martha C. Nason, Robert A. Seder, Richard A. Koup, Norman L. Letvin, Srinivas S. Rao, Gary J. Nabel, John R. Mascola

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)502-508
Number of pages7
JournalNature
Volume505
Issue number7484
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • General

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    Roederer, M., Keele, B. F., Schmidt, S. D., Mason, R. D., Welles, H. C., Fischer, W., Labranche, C., Foulds, K. E., Louder, M. K., Yang, Z. Y., Todd, J. P. M., Buzby, A. P., Mach, L. V., Shen, L., Seaton, K. E., Ward, B. M., Bailer, R. T., Gottardo, R., Gu, W., ... Mascola, J. R. (2014). Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV. Nature, 505(7484), 502-508. https://doi.org/10.1038/nature12893