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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
---|
Gilbert, PB | | | | Peterson, ML | | | | Follmann, D | | | | Hudgens, MG | | | | Francis, DP | | | | Gurwith, M | | | | Heyward, WL | | | | Jobes, DV | | | | Popovic, V | | | | Self, SG | | | | Sinangil, F | | | | Burke, D | donburke@pitt.edu | DONBURKE | | Berman, PW | | | |
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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: |
22 Jun 2021 13:56 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/24315 |
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