Volume 505 Number 7484 pp453-580 23 January 2014
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 et al.
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.