title: Higher T-Cell Responses Induced by DNA/rAd5 HIV-1 Preventive Vaccine Are Associated With Lower HIV-1 Infection Risk in an Efficacy Trial.
abstract: It is important to identify vaccine-induced immune responses that predict the preventative efficacy of a human immunodeficiency virus (HIV)-1 vaccine. We assessed T-cell response markers as correlates of risk in the HIV Vaccine Trials Network (HVTN) 505 HIV-1 vaccine efficacy trial.
  
  
  
  2504 participants were randomized to DNA/rAd5 vaccine or placebo, administered at weeks 0, 4, 8, and 24. Peripheral blood mononuclear cells were obtained at week 26 from all 25 primary endpoint vaccine cases and 125 matched vaccine controls, and stimulated with vaccine-insert-matched peptides. Primary variables were total HIV-1-specific CD4+ T-cell magnitude and Env-specific CD4+ polyfunctionality. Four secondary variables were also assessed. Immune responses were evaluated as predictors of HIV-1 infection among vaccinees using Cox proportional hazards models. Machine learning analyses identified immune response combinations best predicting HIV-1 infection.
  
  
  
  We observed an unexpectedly strong inverse correlation between Env-specific CD8+ immune response magnitude and HIV-1 infection risk (hazard ratio [HR] = 0.18 per SD increment; P = .04) and between Env-specific CD8+ polyfunctionality and infection risk (HR = 0.34 per SD increment; P < .01).
  
  
  
  Further research is needed to determine if these immune responses are predictors of vaccine efficacy or markers of natural resistance to HIV-1 infection.
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Holly E
authors.initials: HE
authors.lastname: Janes
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Kristen W
authors.initials: KW
authors.lastname: Cohen
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Brittany
authors.initials: B
authors.lastname: Sanchez
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: John
authors.initials: J
authors.lastname: Hural
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Magaret
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Shelly
authors.initials: S
authors.lastname: Karuna
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Carter
authors.initials: C
authors.lastname: Bentley
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Raphael
authors.initials: R
authors.lastname: Gottardo
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Greg
authors.initials: G
authors.lastname: Finak
authors.affiliation: The Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Douglas
authors.initials: D
authors.lastname: Grove
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Mingchao
authors.initials: M
authors.lastname: Shen
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, Georgia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.affiliation: Laboratory of Infectious Disease Prevention, New York Blood Center, New York.
authors.forename: Beryl
authors.initials: B
authors.lastname: Koblin
authors.affiliation: Departments of Medicine and Epidemiology/Biostatistics, University of California San Francisco.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Buchbinder
authors.affiliation: University of Rochester Medical Center, School of Medicine and Dentistry, New York.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.affiliation: Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Adams
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland; and.
authors.forename: Chuka
authors.initials: C
authors.lastname: Anude
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.affiliation: Division of Infectious Diseases, Columbia University College of Physicians and Surgeons, New York.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sobieszczyk
authors.affiliation: Division of Infectious Diseases, Columbia University College of Physicians and Surgeons, New York.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Hammer
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D000704:Analysis of Variance; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019295:Computational Biology; D016207:Cytokines / Q000276:immunology; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D000069550:Machine Learning; D012306:Risk
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines
keywords: HIV-1 vaccine; HVTN 505 vaccine efficacy trial; T-cell immunogenicity; T-cell polyfunctionality; correlates of risk; intracellular cytokine staining; machine learning analyses; vaccine-induced immune response.