title: Safety and immunogenicity of a replication-incompetent adenovirus type 5 HIV-1 clade B gag/pol/nef vaccine in healthy adults.
abstract: BACKGROUND
  The safety and immunogenicity of the MRK adenovirus type 5 human immunodeficiency virus type 1 clade B gag/pol/nef vaccine, a replication-incompetent adenovirus type 5-vectored vaccine designed to elicit cell-mediated immunity against conserved human immunodeficiency virus proteins, was assessed in a phase 1 trial.
  
  
  METHODS
  Healthy adults not infected with human immunodeficiency virus were enrolled in a multicenter, dose-escalating, blind, placebo-controlled study to evaluate a 3-dose homologous prime-boost regimen of the trivalent MRK adenovirus type 5 human immunodeficiency virus type 1 vaccine containing from 3 x 10(6) to 1 x 10(11) viral particles per 1-mL dose administered on day 1, during week 4 and during week 26. Adverse events were recorded for 29 days after each intradeltoid injection. The primary immunogenicity end point was the proportion of study participants with a positive unfractionated Gag-, Pol-, or Nef-specific interferon-gamma enzyme-linked immunosorbent spot response measured 4 weeks after administration of the last dose.
  
  
  RESULTS
  Of 259 randomized individuals, 257 (99%) received > or = 1 dose of vaccine or placebo and were included in the safety analyses. Enzyme-linked immunosorbent spot results were available for 217 study participants (84%) at week 30. No serious vaccine-related adverse events occurred. No study participant discontinued participation because of vaccine-related adverse events. The frequency of injection-site reactions was dose dependent. Vaccine doses of > or = 3 x 10(9) viral particles elicited positive enzyme-linked immunosorbent spot responses to > or = 1 vaccine component in > 60% of recipients. High baseline antibody titers against adenovirus type 5 diminished enzyme-linked immunosorbent spot responses at all doses except the 3 x 10(10) viral particle dose.
  
  
  CONCLUSIONS
  The vaccine was generally well tolerated and induced cell-mediated immune responses against human immunodeficiency virus type 1 peptides in most healthy adults. Despite these findings, vaccination in a proof-of-concept trial with use of this vaccine was discontinued because of lack of efficacy.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. fpriddy@emory.edu
authors.forename: Frances H
authors.initials: FH
authors.lastname: Priddy
authors.forename: Deborah
authors.initials: D
authors.lastname: Brown
authors.forename: James
authors.initials: J
authors.lastname: Kublin
authors.forename: Kathleen
authors.initials: K
authors.lastname: Monahan
authors.forename: David P
authors.initials: DP
authors.lastname: Wright
authors.forename: Jacob
authors.initials: J
authors.lastname: Lalezari
authors.forename: Steven
authors.initials: S
authors.lastname: Santiago
authors.forename: Michael
authors.initials: M
authors.lastname: Marmor
authors.forename: Michelle
authors.initials: M
authors.lastname: Lally
authors.forename: Richard M
authors.initials: RM
authors.lastname: Novak
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Brown
authors.forename: Priya
authors.initials: P
authors.lastname: Kulkarni
authors.forename: Sheri A
authors.initials: SA
authors.lastname: Dubey
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Kierstead
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Robin
authors.initials: R
authors.lastname: Mogg
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
authors.forename: Randi Y
authors.initials: RY
authors.lastname: Leavitt
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.forename: Devan V
authors.initials: DV
authors.lastname: Mehrotra
authors.forename: Erin
authors.initials: E
authors.lastname: Quirk
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000256:Adenoviridae; D000328:Adult; D005260:Female; D015685:Fusion Proteins, gag-pol / Q000276:immunology; D015750:Genes, gag; D015751:Genes, pol; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D012449:Safety; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015685:Fusion Proteins, gag-pol; D015483:HIV Antibodies; D019444:Vaccines, DNA