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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Haynes, BF; Gilbert, PB; McElrath, MJ; Zolla-Pazner, S; Tomaras, GD; Alam, SM; Evans, DT; Montefiori, DC; Karnasuta, C; Sutthent, R; Liao, H-X; DeVico, AL; Lewis, GK; Williams, C; Pinter, A; Fong, Y; Janes, H; DeCamp, A; Huang, Y; Rao, M; Billings, E; 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

Published Date

  • April 5, 2012

Published In

Volume / Issue

  • 366 / 14

Start / End Page

  • 1275 - 1286

PubMed ID

  • 22475592

Pubmed Central ID

  • 22475592

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa1113425

Language

  • eng

Conference Location

  • United States