Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.
Published
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
- Alam, S. Munir
- Denny, Thomas Norton
- Ferrari, Guido
- LaBranche, Celia Crane
- Montefiori, David Charles
- Tomaras, Georgia Doris
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 2014
Published In
Volume / Issue
- 505 / 7484
Start / End Page
- 502 - 508
PubMed ID
- 24352234
Pubmed Central ID
- 24352234
Electronic International Standard Serial Number (EISSN)
- 1476-4687
International Standard Serial Number (ISSN)
- 0028-0836
Digital Object Identifier (DOI)
- 10.1038/nature12893
Language
- eng