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

TitleImmune-correlates analysis of an HIV-1 vaccine efficacy trial.
Publication TypeJournal Article
Year of Publication2012
AuthorsHaynes BF, Gilbert PB, McElrath JM, Zolla-Pazner S, Tomaras GD, Alam MS, Evans DT, Montefiori DC, Karnasuta C, Sutthent R, Liao H-X, DeVico AL, Lewis GK, Williams C, Pinter A, Fong Y, Janes H, DeCamp AC, Huang Y, Rao M, Billings EA, Karasavvas N, Robb ML, Ngauy V, de Souza MS, Paris R, Ferrari G, Bailer RT, Soderberg KA, Andrews C, Berman PW, Frahm N, De Rosa SC, Alpert MD, Yates NL, Shen X, Koup RA, Pitisuttithum P, Kaewkungwal J, Nitayaphan S, Rerks-Ngarm S, Michael NL, Kim JH
JournalN Engl J Med
Volume366
Issue14
Pagination1275-86
Date Published2012 Apr 5
ISSN1533-4406
KeywordsAdult, AIDS Vaccines, Case-Control Studies, Follow-Up Studies, HIV Antibodies, HIV Infections, HIV-1, Humans, Immunoglobulin A, Multivariate Analysis, Odds Ratio, Regression Analysis, Risk, Treatment Outcome
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 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.

DOI10.1056/NEJMoa1113425
Alternate JournalN. Engl. J. Med.
PubMed ID22475592