@article{2257e5328ecf4ea0bd1ca7b657b1e4e9,
title = "Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV",
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.",
author = "Mario Roederer and Keele, {Brandon F.} and Schmidt, {Stephen D.} and Mason, {Rosemarie D.} and Welles, {Hugh C.} and Will Fischer and Celia Labranche and Foulds, {Kathryn E.} and Louder, {Mark K.} and Yang, {Zhi Yong} and Todd, {John Paul M.} and Buzby, {Adam P.} and Mach, {Linh V.} and Ling Shen and Seaton, {Kelly E.} and Ward, {Brandy M.} and Bailer, {Robert T.} and Raphael Gottardo and Wenjuan Gu and Guido Ferrari and Alam, {S. Munir} and Denny, {Thomas N.} and Montefiori, {David C.} and Tomaras, {Georgia D.} and Korber, {Bette T.} and Nason, {Martha C.} and Seder, {Robert A.} and Koup, {Richard A.} and Letvin, {Norman L.} and Rao, {Srinivas S.} and Nabel, {Gary J.} and Mascola, {John R.}",
note = "Funding Information: Acknowledgements We thank the following individuals: W. Shi, L. Wu, S.-Y. Ko, L. Wang and W.-P. Kong for immunogen construction; M. M. Donaldson, S.-F. Kao, D. Quinn, J. Owuor, K. Denison, H. Balachandran, C. Luedemann, W. T. Williams, G. Overman, A. Deal,C.Brinkley and L. Racz for technical assistance with immunology assays; A. Ault for assistance managing NHP studies; S. O{\textquoteright}Connor for deep-sequencing data; M. Seaman for providing plasmids encoding E660 envelopes; F. McCutchan, J. Overbaugh and J. Kim for HIV-1 strains; and P. Gilbert for advice with using the Aalen and Johansen model. This work was supported by the Intramural Research Program of the Vaccine Research Center, NIAID, NIH; by NIH contracts HHSN261200800001E (B.F.K.,W.G.)andHHSN27201100016C(D.C.M.);byNIHgrantAI100645(B.T.K.,W.F.); and by the Bill and Melinda Gates Foundation grant OPP1032317.",
year = "2014",
doi = "10.1038/nature12893",
language = "English (US)",
volume = "505",
pages = "502--508",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7484",
}