title: Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector.
abstract: BACKGROUND
  The development of an effective human immunodeficiency virus (HIV) vaccine is a high global priority. Here, we report the safety, tolerability, and immunogenicity of a replication-defective recombinant adenovirus serotype 5 (rAd5) vector HIV-1 candidate vaccine.
  
  
  METHODS
  The vaccine is a mixture of 4 rAd5 vectors that express HIV-1 subtype B Gag-Pol fusion protein and envelope (Env) from subtypes A, B, and C. Healthy, uninfected adults were randomized to receive 1 intramuscular injection of placebo (n=6) or vaccine at dose levels of 10(9) (n=10), 10(10) (n=10), or 10(11) (n=10) particle units and were followed for 24 weeks to assess immunogenicity and safety.
  
  
  RESULTS
  The vaccine was well tolerated but was associated with more reactogenicity at the highest dose. At week 4, vaccine antigen-specific T cell responses were detected in 28 (93.3%) and 18 (60%) of 30 vaccine recipients for CD4(+) and CD8(+) T cells, respectively, by intracellular cytokine staining assay and in 22 (73%) of 30 vaccine recipients by enzyme-linked immunospot assay. Env-specific antibody responses were detected in 15 (50%) of 30 vaccine recipients by enzyme-linked immunosorbant assay and in 28 (93.3%) of 30 vaccine recipients by immunoprecipitation followed by Western blotting. No neutralizing antibody was detected.
  
  
  CONCLUSIONS
  A single injection induced HIV-1 antigen-specific CD4(+) T cell, CD8(+) T cell, and antibody responses in the majority of vaccine recipients. This multiclade rAd5 HIV-1 vaccine is now being evaluated in combination with a multiclade HIV-1 DNA plasmid vaccine.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3017, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Catanzaro
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.forename: Zoe
authors.initials: Z
authors.lastname: Moodie
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.forename: Julie E
authors.initials: JE
authors.lastname: Martin
authors.forename: Laura
authors.initials: L
authors.lastname: Novik
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Chakrabarti
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Butman
authors.forename: Jason G D
authors.initials: JG
authors.lastname: Gall
authors.forename: C Richter
authors.initials: CR
authors.lastname: King
authors.forename: Charla A
authors.initials: CA
authors.lastname: Andrews
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sheets
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Gomez
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000260:Adenoviruses, Human / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D000918:Antibody Specificity; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015685:Fusion Proteins, gag-pol / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D009325:Nausea / Q000209:etiology*; D011995:Recombination, Genetic; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D016207:Cytokines; D015685:Fusion Proteins, gag-pol; D015686:Gene Products, env; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1