title: First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001).
abstract: BACKGROUND
  We report the first-in-human safety and immunogenicity assessment of a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in humans.
  
  
  METHODS
  Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Five groups of 12 subjects received 10(9)-10(11) vp of the Ad26-EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks 0, 4, and 24. Safety and immunogenicity were assessed.
  
  
  RESULTS
  Self-limited reactogenicity was observed after the initial immunization at the highest (10(11) vp) dose. No product-related SAEs were observed. All subjects who received the Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in the 10(9), 10(10), 10(11) vp 3-dose and the 10(10) and 5 × 10(10) vp 2-dose groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655 and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/10(6) peripheral blood mononuclear cells, respectively.
  
  
  CONCLUSIONS
  This Ad26 vectored vaccine was generally safe and immunogenic at all doses tested. Reactogenicity was minimal with doses of 5 × 10(10) vp or less. Ad26 is a promising new vaccine vector for HIV-1.
  
  
  BACKGROUND
  NCT00618605.
authors.affiliation: Brigham and Women's Hospital, Rockville, Maryland, USA. lbaden@partners.org
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Walsh
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Robert P
authors.initials: RP
authors.lastname: Tucker
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: Krause
authors.forename: Alka
authors.initials: A
authors.lastname: Patel
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Jane
authors.initials: J
authors.lastname: Kleinjan
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Yanosick
authors.forename: James
authors.initials: J
authors.lastname: Perry
authors.forename: Elise
authors.initials: E
authors.lastname: Zablowsky
authors.forename: Peter
authors.initials: P
authors.lastname: Abbink
authors.forename: Lauren
authors.initials: L
authors.lastname: Peter
authors.forename: M Justin
authors.initials: MJ
authors.lastname: Iampietro
authors.forename: Ann
authors.initials: A
authors.lastname: Cheung
authors.forename: Maria G
authors.initials: MG
authors.lastname: Pau
authors.forename: Mo
authors.initials: M
authors.lastname: Weijtens
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Edith
authors.initials: E
authors.lastname: Swann
authors.forename: Mark
authors.initials: M
authors.lastname: Wolff
authors.forename: Hayley
authors.initials: H
authors.lastname: Loblein
authors.forename: Raphael
authors.initials: R
authors.lastname: Dolin
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000260:Adenoviruses, Human / Q000145:classification / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D014614:Vaccines, Synthetic