Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIVmac251 acquisition in an immunization regimen that mimics the RV-144 thai trial

Poonam Pegu, Monica Vaccari, Shari Gordon, Brandon F. Keele, Melvin Doster, Yongjun Guan, Guido Ferrari, Ranajit Pal, Maria Grazia Ferrari, Stephen Whitney, Lauren Hudacik, Erik Billings, Mangala Rao, David Montefiori, Georgia Tomaras, S. Munir Alam, Claudio Fenizia, Jeffrey D. Lifson, Donald Stablein, Jim TartagliaNelson Michael, Jerome Kim, David Venzon, Genoveffa Franchini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8+ T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIVmac251 that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4+ and CD8+ T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIVmac251 acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIVmac251-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIVmac251 infectivity in cells that express high levels of α4β7 integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.

Original languageEnglish
Pages (from-to)1708-1719
Number of pages12
JournalJournal of Virology
Volume87
Issue number3
DOIs
StatePublished - Feb 2013
Externally publishedYes

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