Immune-correlates analysis of an HIV-1 vaccine efficacy trial

Barton F. Haynes*, Peter B. Gilbert, M. Juliana McElrath, Susan Zolla-Pazner, Georgia D. Tomaras, S. Munir Alam, David T. Evans, David C. Montefiori, Chitraporn Karnasuta, Ruengpueng Sutthent, Hua Xin Liao, Anthony L. DeVico, George K. Lewis, Constance Williams, Abraham Pinter, Youyi Fong, Holly Janes, Allan DeCamp, Yunda Huang, Mangala RaoErik Billings, Nicos Karasavvas, Merlin L. Robb, Viseth Ngauy, Mark S. De Souza, Robert Paris, Guido Ferrari, Robert T. Bailer, Kelly A. Soderberg, Charla Andrews, Phillip W. Berman, Nicole Frahm, Stephen C. De Rosa, Michael D. Alpert, Nicole L. Yates, Xiaoying Shen, Richard A. Koup, Punnee Pitisuttithum, Jaranit Kaewkungwal, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Nelson L. Michael, Jerome H. Kim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1529 Scopus citations

Abstract

BACKGROUND: In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a case-control analysis to identify antibody and cellular immune correlates of infection risk. METHODS: In pilot studies conducted with RV144 blood samples, 17 antibody or cellular assays met prespecified criteria, of which 6 were chosen for primary analysis to determine the roles of T-cell, IgG antibody, and IgA antibody responses in the modulation of infection risk. Assays were performed on samples from 41 vaccinees who became infected and 205 uninfected vaccinees, obtained 2 weeks after final immunization, to evaluate whether immune-response variables predicted HIV-1 infection through 42 months of follow-up. RESULTS: Of six primary variables, two correlated significantly with infection risk: the binding of IgG antibodies to variable regions 1 and 2 (V1V2) of HIV-1 envelope proteins (Env) correlated inversely with the rate of HIV-1 infection (estimated odds ratio, 0.57 per 1-SD increase; P = 0.02; q = 0.08), and the binding of plasma IgA antibodies to Env correlated directly with the rate of infection (estimated odds ratio, 1.54 per 1-SD increase; P = 0.03; q = 0.08). Neither low levels of V1V2 antibodies nor high levels of Env-specific IgA antibodies were associated with higher rates of infection than were found in the placebo group. Secondary analyses suggested that Envspecific IgA antibodies may mitigate the effects of potentially protective antibodies. CONCLUSIONS:This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Envspecific IgA antibodies may have mitigated the effects of protective antibodies. Vaccines that are designed to induce higher levels of V1V2 antibodies and lower levels of Env-specific IgA antibodies than are induced by the RV144 vaccine may have improved efficacy against HIV-1 infection.

Original languageEnglish
Pages (from-to)1275-1286
Number of pages12
JournalNew England Journal of Medicine
Volume366
Issue number14
DOIs
StatePublished - 5 Apr 2012
Externally publishedYes

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