title: Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine induced immune responses.
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-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.
  
  
  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).
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Hopkins
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Fatima
authors.initials: F
authors.lastname: Laher
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Kennedy
authors.initials: K
authors.lastname: Otwombe
authors.affiliation: Aurum Institute for Health Research, Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Gavin
authors.initials: G
authors.lastname: Churchyard
authors.affiliation: Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.affiliation: HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: DeRosa
authors.affiliation: Medunsa HIV Clinical Research Unit, University of Limpopo, Pretoria, South Africa.
authors.forename: Maphoshane
authors.initials: M
authors.lastname: Nchabeleng
authors.affiliation: Centre for AIDS Programme for Research in South Africa & Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.affiliation: HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Kublin
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Glenda
authors.initials: G
authors.lastname: Gray
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000256:Adenoviridae; D003710:Demography; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015488:HIV Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus
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