Dataset Information
Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine induced immune responses.
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ABSTRACT: Background
Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses.Methods
Vaccine-induced immunogenicity was ascertained by interferon-? ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors.Results
Of the 186 participants, 53.7% (n?=?100) were female, median BMI was 22.5 [IQR: 20.4-27.0], 85.5% (n?=?159) were Ad5 seropositive, and 18.8% (n?=?35) drank heavily. All vaccine recipients responded to both clade B (n?=?87; 47%) and/or C (n?=?74; 40%), p?=?0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p?=?0.0159], overweight/obese BMI (AOR: 0.186; p?=?0.0452), and heavy drinking (AOR: 0.270; p?=?0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p?=?0.0500).Conclusions
Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity).
SUBMITTER: Hopkins KL
PROVIDER: S-EPMC4121165 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine induced immune responses.
PloS one 20140804 8
<h4>Background</h4>Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses.<h4>Methods</h4>Vaccine-induced immunogenic ...[more]