title: Safety and immunogenicity study of Multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa.
abstract: BACKGROUND
  We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults.
  
  
  RESULTS
  Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×10(10) or 1×10(11) particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone.
  
  
  CONCLUSIONS
  The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00124007.
authors.affiliation: Kenya AIDS Vaccine Initiative (KAVI), Nairobi, Kenya.
authors.forename: Walter
authors.initials: W
authors.lastname: Jaoko
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.forename: Kayitesi
authors.initials: K
authors.lastname: Kayitenkore
authors.forename: Gloria
authors.initials: G
authors.lastname: Omosa-Manyonyi
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.forename: Soe
authors.initials: S
authors.lastname: Than
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Adams
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.forename: Carol
authors.initials: C
authors.lastname: Smith
authors.forename: Len
authors.initials: L
authors.lastname: Dally
authors.forename: Bashir
authors.initials: B
authors.lastname: Farah
authors.forename: Omu
authors.initials: O
authors.lastname: Anzala
authors.forename: Claude M
authors.initials: CM
authors.lastname: Muvunyi
authors.forename: Jean
authors.initials: J
authors.lastname: Bizimana
authors.forename: Tony
authors.initials: T
authors.lastname: Tarragona-Fiol
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bergin
authors.forename: Peter
authors.initials: P
authors.lastname: Hayes
authors.forename: Martin
authors.initials: M
authors.lastname: Ho
authors.forename: Kelley
authors.initials: K
authors.lastname: Loughran
authors.forename: Wendy
authors.initials: W
authors.lastname: Komaroff
authors.forename: Gwynneth
authors.initials: G
authors.lastname: Stevens
authors.forename: Helen
authors.initials: H
authors.lastname: Thomson
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Boaz
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Cox
authors.forename: Claudia
authors.initials: C
authors.lastname: Schmidt
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: Patricia
authors.initials: P
authors.lastname: Fast
authors.forename: Job
authors.initials: J
authors.lastname: Bwayo
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects* / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005822:Genetic Vectors / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D008297:Male; D008875:Middle Aged; D019444:Vaccines, DNA / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus