title: Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV-1 Prevention: A Randomized Trial.
abstract: BACKGROUND
  A prophylactic HIV-1 vaccine is a global health priority.
  
  
  OBJECTIVE
  To assess a novel vaccine platform as a prophylactic HIV-1 regimen.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149).
  
  
  METHODS
  United States, East Africa, and South Africa.
  
  
  METHODS
  Healthy adults without HIV infection.
  
  
  METHODS
  2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations.
  
  
  METHODS
  Safety and immunogenicity and the effect of baseline vector immunity.
  
  
  RESULTS
  217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States.
  
  
  CONCLUSIONS
  Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown.
  
  
  CONCLUSIONS
  Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response.
  
  
  BACKGROUND
  International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.forename: Gaudensia
authors.initials: G
authors.lastname: Mutua
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Glenda
authors.initials: G
authors.lastname: Gray
authors.forename: Liesl
authors.initials: L
authors.lastname: Page-Shipp
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Walsh
authors.forename: Julien
authors.initials: J
authors.lastname: Nyombayire
authors.forename: Omu
authors.initials: O
authors.lastname: Anzala
authors.forename: Surita
authors.initials: S
authors.lastname: Roux
authors.forename: Fatima
authors.initials: F
authors.lastname: Laher
authors.forename: Craig
authors.initials: C
authors.lastname: Innes
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Yehuda Z
authors.initials: YZ
authors.lastname: Cohen
authors.forename: Lauren
authors.initials: L
authors.lastname: Peter
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Peter
authors.initials: P
authors.lastname: Hayes
authors.forename: Edith
authors.initials: E
authors.lastname: Swann
authors.forename: Nicole
authors.initials: N
authors.lastname: Grunenberg
authors.forename: Maria
authors.initials: M
authors.lastname: Grazia-Pau
authors.forename: Mo
authors.initials: M
authors.lastname: Weijtens
authors.forename: Jerry
authors.initials: J
authors.lastname: Sadoff
authors.forename: Len
authors.initials: L
authors.lastname: Dally
authors.forename: Angela
authors.initials: A
authors.lastname: Lombardo
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.forename: Raphael
authors.initials: R
authors.lastname: Dolin
authors.forename: Patricia
authors.initials: P
authors.lastname: Fast
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Dagna S
authors.initials: DS
authors.lastname: Laufer
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects* / Q000276:immunology*; D000256:Adenoviridae; D000293:Adolescent; D000328:Adult; D000351:Africa, Eastern; D000917:Antibody Formation; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008297:Male; D008875:Middle Aged; D013019:South Africa; D014481:United States; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines
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