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
PB Gilbert, ML Peterson, D Follmann… - The Journal of …, 2005 - academic.oup.com
The Journal of infectious diseases, 2005•academic.oup.com
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 …
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 …
Abstract
BackgroundAn 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
MethodsWithin 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
ResultsPeak 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
ConclusionsDespite 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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