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.
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 log(10) higher neutralization titer against HIV-1(MN), 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.
Gilbert
Peter B
PB
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Peterson
Michael L
ML
Follmann
Dean
D
Hudgens
Michael G
MG
Francis
Donald P
DP
Gurwith
Marc
M
Heyward
William L
WL
Jobes
David V
DV
Popovic
Vladimir
V
Self
Steven G
SG
Sinangil
Faruk
F
Burke
Donald
D
Berman
Phillip W
PW
D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D005006:Ethnicity; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000276:immunology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic