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1 March 2005

Volume 191, Number 5
The Journal of Infectious Diseases 2005;191:666–677
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19105-0004$15.00
DOI: 10.1086/428405
MAJOR ARTICLE

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

Peter B. Gilbert,1

Michael L. Peterson,2

Dean Follmann,4

Michael G. Hudgens,6,a

Donald P. Francis,3,a

Marc Gurwith,2

William L. Heyward,2,a

David V. Jobes,2

Vladimir Popovic,2,a

Steven G. Self,1

Faruk Sinangil,2

Donald Burke,5 and

Phillip W. Berman3,a

1Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington; 2VaxGen and 3Global Solutions for Infectious Diseases, Brisbane, California; 4Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and 5Johns Hopkins Bloomberg University School of Public Health, Baltimore, Maryland; and 6Department of Biostatistics, University of North Carolina, Chapel Hill

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, ; for placebo recipients, ), 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.

Received 13 July 2004; accepted 15 November 2004; electronically published 27 January 2005.

Reprints or correspondence: Dr. Marc Gurwith, VaxGen, 1000 Marina Blvd., Brisbane, CA 94005‐1841 ().

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  • Presented in part: AIDS Vaccine 2003, New York, 18–21 September 2003 (abstract 147).

    Potential conflicts of Interest: M.G., D.V.J., M.L.P., and F.S. are employees of VaxGen; P.W.B., D.P.F., W.L.H., and V.P. are former employees of VaxGen; P.B.G., M.G.H. and S.G.S. have received consulting fees from VaxGen in the past.

    Financial Support: VaxGen; Centers for Disease Control and Prevention; National Institutes of Health; Science Applications International Corporation–Frederick (contract 23XS119).

  • Present affiliations: School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill (M.G.H.); Global Solutions for Infectious Diseases, Brisbane, California (D.P.F. and P.W.B.); Quattro Clinical Research, Oakland, California (W.L.H.); Janssen Ortho, Toronto, Ontario, Canada (V.P.).

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