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Correlation between immunologic responses to a recombinant glycoprotein 120 vaccine and incidence of HIV-1 infection in a phase 3 HIV-1 preventive vaccine trial

Gilbert, PB and Peterson, ML and Follmann, D and Hudgens, MG and Francis, DP and Gurwith, M and Heyward, WL and Jobes, DV and Popovic, V and Self, SG and Sinangil, F and Burke, D and Berman, PW (2005) Correlation between immunologic responses to a recombinant glycoprotein 120 vaccine and incidence of HIV-1 infection in a phase 3 HIV-1 preventive vaccine trial. Journal of Infectious Diseases, 191 (5). 666 - 677. ISSN 0022-1899

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Abstract

Background. An objective of the first efficacy trial of a candidate vaccine containing recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein 120 (rgp120) antigens was to assess correlations between antibody responses to rgp120 and the incidence of HIV-1 infection. Methods. Within the randomized trial (for vaccinees, n = 3598; for placebo recipients, n = 1805), binding and neutralizing antibody responses to rgp120 were quantitated. A case-cohort design was used to study correlations between antibody levels and HIV-1 incidence. Results. Peak antibody levels were significantly inversely correlated with HIV-1 incidence. The relative risk (RR) of infection was 0.63 (95% confidence interval, 0.45-0.89) per log10 higher neutralization titer against HIV-1MN, and the RRs of infection for second-, third-, and fourth-quartile responses of antibody blocking of gp120 binding to soluble CD4 versus first-quartile responses (the lowest responses) were 0.35, 0.28, and 0.22, respectively. Conclusions. Despite inducing a complex, robust immune response, the vaccine was unable to reduce the incidence of HIV-1. Two interpretations of the correlative results are that the levels of antibodies (i) caused both an increased (low responders) and decreased (high responders) risk of HIV-1 acquisition or (ii) represented a correlate of susceptibility to HIV-1 but had no causal effect on susceptibility. Although the data cannot definitively discriminate between these 2 explanations, (ii) appears to be more likely.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gilbert, PB
Peterson, ML
Follmann, D
Hudgens, MG
Francis, DP
Gurwith, M
Heyward, WL
Jobes, DV
Popovic, V
Self, SG
Sinangil, F
Burke, Ddonburke@pitt.eduDONBURKE
Berman, PW
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 1 March 2005
Date Type: Publication
Journal or Publication Title: Journal of Infectious Diseases
Volume: 191
Number: 5
Page Range: 666 - 677
DOI or Unique Handle: 10.1086/428405
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
ISSN: 0022-1899
Date Deposited: 08 May 2015 14:41
Last Modified: 02 Feb 2019 16:57
URI: http://d-scholarship.pitt.edu/id/eprint/24315

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