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 Ferrari, S. 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 and John R. Mascola
Additional contact information
Mario Roederer: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Brandon F. Keele: SAIC-Frederick, Frederick National Laboratory, NIH, Frederick, Maryland 21702, USA
Stephen D. Schmidt: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Rosemarie D. Mason: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Hugh C. Welles: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Will Fischer: Los Alamos National Laboratories
Celia Labranche: Duke University
Kathryn E. Foulds: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Mark K. Louder: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Zhi-Yong Yang: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
John-Paul M. Todd: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Adam P. Buzby: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
Linh V. Mach: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
Ling Shen: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
Kelly E. Seaton: Human Vaccine Institute, Duke University
Brandy M. Ward: Duke University
Robert T. Bailer: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Raphael Gottardo: Fred Hutchison Cancer Research Center
Wenjuan Gu: Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland 20892, USA
Guido Ferrari: Duke University
S. Munir Alam: Human Vaccine Institute, Duke University
Thomas N. Denny: Human Vaccine Institute, Duke University
David C. Montefiori: Duke University
Georgia D. Tomaras: Human Vaccine Institute, Duke University
Bette T. Korber: Los Alamos National Laboratories
Martha C. Nason: Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland 20892, USA
Robert A. Seder: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Richard A. Koup: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Norman L. Letvin: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
Srinivas S. Rao: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
Gary J. Nabel: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
John R. Mascola: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA

Nature, 2014, vol. 505, issue 7484, 502-508

Abstract: 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.

Date: 2014
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DOI: 10.1038/nature12893

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