title: 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.
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 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.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.forename: Michael L
authors.initials: ML
authors.lastname: Peterson
authors.forename: Dean
authors.initials: D
authors.lastname: Follmann
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.forename: Donald P
authors.initials: DP
authors.lastname: Francis
authors.forename: Marc
authors.initials: M
authors.lastname: Gurwith
authors.forename: William L
authors.initials: WL
authors.lastname: Heyward
authors.forename: David V
authors.initials: DV
authors.lastname: Jobes
authors.forename: Vladimir
authors.initials: V
authors.lastname: Popovic
authors.forename: Steven G
authors.initials: SG
authors.lastname: Self
authors.forename: Faruk
authors.initials: F
authors.lastname: Sinangil
authors.forename: Donald
authors.initials: D
authors.lastname: Burke
authors.forename: Phillip W
authors.initials: PW
authors.lastname: Berman
mesh_terms: 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
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic