Lessons from the RV144 Thai Phase III HIV-1 Vaccine Trial and the Search for Correlates of Protection

Author:

Kim Jerome H.1,Excler Jean-Louis12,Michael Nelson L.1

Affiliation:

1. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910;,

2. US Military HIV Research Program, Henry M. Jackson Foundation, Bethesda, Maryland 20817;

Abstract

RV144 remains the only HIV-1 vaccine trial to demonstrate efficacy against HIV-1 acquisition. The prespecified analysis of immune correlates of risk showed that antibodies directed against the V1V2 region of gp120, in particular the IgG1 and IgG3 subclass mediating antibody-dependent cell-mediated cytotoxicity, seem to play a predominant role in protection against HIV-1 acquisition and that plasma envelope (Env)-specific IgA antibodies were directly correlated with risk. RV144 and recent nonhuman primate challenge studies suggest that Env is essential, and perhaps sufficient, to induce protective antibody responses against mucosal HIV-1 acquisition. Follow-up clinical trials are ongoing to further dissect the immune responses elicited by the RV144 ALVAC-HIV and AIDSVAX® B/E regimen. The study of gp120 Env immunogens and immune correlates of risk has resulted in the development of improved antigens. Whether the RV144 immune correlates of risk will generalize to other populations vaccinated with similar immunogens with different modes and intensity of transmission remains to be demonstrated. Efficacy trials are now planned in heterosexual populations in southern Africa and men who have sex with men in Thailand.

Publisher

Annual Reviews

Subject

General Biochemistry, Genetics and Molecular Biology,General Medicine

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