• 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 Rao, Erik 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, and Jerome H Kim.
• Duke University Human Vaccine Institute and the Center for HIV/AIDS Vaccine Immunology, Duke University School of Medicine, Durham, NC 27710, USA. hayne002@mc.duke.edu
• N. Engl. J. Med. 2012 Apr 5; 366 (14): 1275-86.

BackgroundIn 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.MethodsIn 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.ResultsOf 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 Env-specific IgA antibodies may mitigate the effects of potentially protective antibodies.ConclusionsThis immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Env-specific 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.

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