Abstract
BackgroundPhambili, 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.MethodsVaccine-induced immunogenicity was ascertained by interferon-γ 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.ResultsOf 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).ConclusionsSex, 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).
Highlights
Phambili (HVTN 503) was a Phase IIb HIV vaccine efficacy study conducted in South Africa
We investigate predictors associated with the MRK-Adenovirus Type 5 (Ad5) vaccine-specific T-cell immune response for HIV-1 clade B and clade C amongst South African participants in an attempt to further improve upon future HIV vaccine candidates
Our paper describes a subset of enrolled participants, 93 per study arm, assessed for immunogenicity by ELISpot analysis
Summary
Phambili (HVTN 503) was a Phase IIb HIV vaccine efficacy study conducted in South Africa. It investigated the Merck (MRK)-Adenovirus type-5 (Ad5) HIV-1 clade B trivalent HIV vaccine, which contains recombinant Ad5 (rAd5) vectors expressing clade B gag, pol, and nef epitopes [1,2,3]. Vaccine-induced immune responses to HIV-1 may not necessarily equate to protection or risk. It is uncertain which immune responses are required for protection against HIV infection or controlling viremia [4]. 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. We investigated predictors of the vaccine-induced antigen-specific immune responses
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