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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Roederer, M; Keele, BF; Schmidt, SD; Mason, RD; Welles, HC; Fischer, W; Labranche, C; Foulds, KE; Louder, MK; Yang, Z-Y; Todd, J-PM; Buzby, AP; Mach, LV; Shen, L; Seaton, KE; Ward, BM; Bailer, RT; Gottardo, R; Gu, W; Ferrari, G; Alam, SM; Denny, TN; Montefiori, DC; Tomaras, GD; Korber, BT; Nason, MC; Seder, RA; Koup, RA; Letvin, NL; Rao, SS; Nabel, GJ; Mascola, JR

Published Date

  • January 23, 2014

Published In

Volume / Issue

  • 505 / 7484

Start / End Page

  • 502 - 508

PubMed ID

  • 24352234

Pubmed Central ID

  • PMC3946913

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature12893

Language

  • eng

Conference Location

  • England