title: Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083.
abstract: BACKGROUND
  Increasing the breadth of human immunodeficiency virus type 1 (HIV-1) vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HIV Vaccine Trials Network 083 tested whether cellular immune responses with these features are induced by prime-boost strategies, using heterologous vectors, heterologous inserts, or a combination of both.
  
  
  METHODS
  A total of 180 participants were randomly assigned to receive combinations of adenovirus vectors (Ad5 or Ad35) and HIV-1 envelope (Env) gene inserts (clade A or B) in a prime-boost regimen.
  
  
  RESULTS
  T-cell responses to heterologous and homologous insert regimens targeted a similar number of epitopes (ratio of means, 1.0; 95% confidence interval [CI], .6-1.6; P = .91), but heterologous insert regimens induced significantly more epitopes that were shared between EnvA and EnvB than homologous insert regimens (ratio of means, 2.7; 95% CI, 1.2-5.7; P = .01). Participants in the heterologous versus homologous insert groups had T-cell responses that targeted epitopes with greater evolutionary conservation (mean entropy [±SD], 0.32 ± 0.1 bits; P = .003), and epitopes recognized by responders provided higher coverage (49%; P = .035). Heterologous vector regimens had higher numbers of total, EnvA, and EnvB epitopes than homologous vector regimens (P = .02, .044, and .045, respectively).
  
  
  CONCLUSIONS
  These data demonstrate that vaccination with heterologous insert prime boosting increased T-cell responses to shared epitopes, while heterologous vector prime boosting increased the number of T-cell epitopes recognized.
  
  
  BACKGROUND
  NCT01095224.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Walsh
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Moodie
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fiore-Gartland
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgan
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts.
authors.forename: Marissa B
authors.initials: MB
authors.lastname: Wilck
authors.affiliation: Columbia University, New York.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Hammer
authors.affiliation: San Francisco Department of Public Health, California.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Buchbinder
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.affiliation: University of Alabama, Birmingham.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.affiliation: Emory University, Decatur, Georgia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.affiliation: University of Rochester, New York.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.affiliation: Division of AIDS.
authors.forename: Edith M
authors.initials: EM
authors.lastname: Swann
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Shannon
authors.initials: S
authors.lastname: Grant
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Hasan
authors.initials: H
authors.lastname: Ahmed
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Li
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Tomer
authors.initials: T
authors.lastname: Hertz
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Self
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: David
authors.initials: D
authors.lastname: Friedrich
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center Department of Global Health, University of Washington, Seattle.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center Department of Global Health, University of Washington, Seattle Departments of Medicine and Laboratory Medicine, University of Washington, Seattle.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: John
authors.initials: J
authors.lastname: Hural
authors.affiliation: Dale and Betty Bumpers Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.affiliation: University of Rochester, New York.
authors.forename: Xia
authors.initials: X
authors.lastname: Jin
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D004337:Drug Carriers; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: HIV-1; adenovirus; clinical trial; epitope mapping; immunogenicity; prime-boost; vaccines