Skip to main content

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

Publication ,  Journal Article
Haynes, BF; Gilbert, PB; McElrath, MJ; Zolla-Pazner, S; Tomaras, GD; Alam, SM; Evans, DT; Montefiori, DC; Karnasuta, C; Sutthent, R; Liao, H-X ...
Published in: N Engl J Med
April 5, 2012

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

April 5, 2012

Volume

366

Issue

14

Start / End Page

1275 / 1286

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Risk
  • Regression Analysis
  • Odds Ratio
  • Multivariate Analysis
  • Immunoglobulin A
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Haynes, B. F., Gilbert, P. B., McElrath, M. J., Zolla-Pazner, S., Tomaras, G. D., Alam, S. M., … Kim, J. H. (2012). Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med, 366(14), 1275–1286. https://doi.org/10.1056/NEJMoa1113425
Haynes, Barton F., Peter B. Gilbert, M Juliana McElrath, Susan Zolla-Pazner, Georgia D. Tomaras, S Munir Alam, David T. Evans, et al. “Immune-correlates analysis of an HIV-1 vaccine efficacy trial.N Engl J Med 366, no. 14 (April 5, 2012): 1275–86. https://doi.org/10.1056/NEJMoa1113425.
Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012 Apr 5;366(14):1275–86.
Haynes, Barton F., et al. “Immune-correlates analysis of an HIV-1 vaccine efficacy trial.N Engl J Med, vol. 366, no. 14, Apr. 2012, pp. 1275–86. Pubmed, doi:10.1056/NEJMoa1113425.
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. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012 Apr 5;366(14):1275–1286.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

April 5, 2012

Volume

366

Issue

14

Start / End Page

1275 / 1286

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Risk
  • Regression Analysis
  • Odds Ratio
  • Multivariate Analysis
  • Immunoglobulin A
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies