BACKGROUND: An objective of the first efficacy trial of a candidate vaccine containing recombinant human immunodeficiency virus (HIV) type 1envelope 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.
RCT Entities:
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.
Authors: Robert Pejchal; Laura M Walker; Robyn L Stanfield; Sanjay K Phogat; Wayne C Koff; Pascal Poignard; Dennis R Burton; Ian A Wilson Journal: Proc Natl Acad Sci U S A Date: 2010-06-02 Impact factor: 11.205
Authors: Nicos Karasavvas; Erik Billings; Mangala Rao; Constance Williams; Susan Zolla-Pazner; Robert T Bailer; Richard A Koup; Sirinan Madnote; Duangnapa Arworn; Xiaoying Shen; Georgia D Tomaras; Jeffrey R Currier; Mike Jiang; Craig Magaret; Charla Andrews; Raphael Gottardo; Peter Gilbert; Timothy J Cardozo; Supachai Rerks-Ngarm; Sorachai Nitayaphan; Punnee Pitisuttithum; Jaranit Kaewkungwal; Robert Paris; Kelli Greene; Hongmei Gao; Sanjay Gurunathan; Jim Tartaglia; Faruk Sinangil; Bette T Korber; David C Montefiori; John R Mascola; Merlin L Robb; Barton F Haynes; Viseth Ngauy; Nelson L Michael; Jerome H Kim; Mark S de Souza Journal: AIDS Res Hum Retroviruses Date: 2012-10-04 Impact factor: 2.205
Authors: Norman G Jones; Allan DeCamp; Peter Gilbert; Michael L Peterson; Marc Gurwith; Huyen Cao Journal: Vaccine Date: 2008-12-09 Impact factor: 3.641