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


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.
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.
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.
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.


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  • Authors

    Haynes BF

    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

    Gilbert PB

    McElrath MJ

    Zolla-Pazner S

    Tomaras GD

    Alam SM

    Evans DT

    Montefiori DC

    Karnasuta C

    Sutthent R

    Liao HX

    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


    The New England journal of medicine 366:14 2012 Apr 5 pg 1275-86


    AIDS Vaccines
    Case-Control Studies
    Follow-Up Studies
    HIV Antibodies
    HIV Infections
    Immunoglobulin A
    Multivariate Analysis
    Odds Ratio
    Regression Analysis
    Treatment Outcome

    Pub Type(s)

    Evaluation Studies
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.



    PubMed ID