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 Env-specific 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 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. The views expressed in this article are those of the authors and should not be construed as official or as representing the views of the Department of Health and Human Services, the National Institute of Allergy and Infectious Diseases (NIAID), the Department of Defense, the Department of the Army, or the Department of Veterans Affairs. Supported in part by grants from the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (to Drs. Haynes, Koup, and Montefiori); an interagency agreement between the U.S. Army Medical Research and Materiel Command and the NIAID (Y1-AI-2642-12); a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the Department of Defense (W81XWH-07-2-0067); and grants from the NIAID to the Center for HIV/AIDS Vaccine Immunology (U01-AI-067854) and the HIV Vaccine Trials Network Laboratory Program (UM1-AI-068618).
