title: Safety and Immunogenicity of the MRKAd5 gag HIV Type 1 Vaccine in a Worldwide Phase 1 Study of Healthy Adults.
abstract: The safety and immunogenicity of the MRK adenovirus type 5 (Ad5) HIV-1 clade B gag vaccine was assessed in an international Phase I trial. Three-hundred and sixty healthy HIV-uninfected adults were enrolled on five continents. Subjects received placebo or 1 × 109or 1 × 1010viral particles (vp) per dose of the MRKAd5 HIV-1 gag vaccine at day 1, week 4, and week 26. Immunogenicity was evaluated using an IFN-γ ELISPOT gag 15-mer assay with positive responses defined as ≥55 SFC/106PBMCs and ≥4-fold over mock control. The vaccine was well tolerated. The most common adverse events were injection site reactions, headache, pyrexia, diarrhea, fatigue, and myalgia. At week 30, geometric mean ELISPOT responses were 24, 114, and 226 SFC/106PBMCs in the placebo, 1 × 109vp/dose, and 1 × 1010vp/dose groups, respectively. Overall, responses to 1 × 1010vp were 85% and 68% in subjects with low (≤200) and high (>200) baseline Ad5 titers, respectively. The MRKAd5 HIV-1 gag vaccine was immunogenic in diverse geographic regions. Gag ELISPOT responses were greater in the 1 × 1010vp/dose groups than in the 1 × 109vp/dose groups. Data from this first international study indicate that adenovirus-vectored vaccines are well tolerated and may be immunogenic in subjects from regions with high prevalence of preexisting Ad5 immunity.
authors.affiliation: Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
authors.forename: Ouzama
authors.initials: O
authors.lastname: Nicholson
authors.affiliation: Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
authors.forename: Fay
authors.initials: F
authors.lastname: DiCandilo
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: James
authors.initials: J
authors.lastname: Kublin
authors.affiliation: Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
authors.forename: Erin
authors.initials: E
authors.lastname: Quirk
authors.affiliation: Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
authors.forename: Michelle
authors.initials: M
authors.lastname: Miller
authors.affiliation: University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Glenda
authors.initials: G
authors.lastname: Gray
authors.affiliation: Weill Cornell Medical College, New York, New York.
authors.forename: Jean
authors.initials: J
authors.lastname: Pape
authors.affiliation: Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.affiliation: Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
authors.forename: Devan V
authors.initials: DV
authors.lastname: Mehrotra
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Steven
authors.initials: S
authors.lastname: Self
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Katherine
authors.initials: K
authors.lastname: Turner
authors.affiliation: Asociacion Civil Impacta Salud y Educacion, Lima, Peru and Investigaciones Medicas en Salu, Immensa, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: Mahidol University, Bangkok, Thailand.
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.|University of Washington, Seattle, Washington.
authors.forename: Ann
authors.initials: A
authors.lastname: Duerr
authors.affiliation: Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
authors.forename: Sheri
authors.initials: S
authors.lastname: Dubey
authors.affiliation: Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kierstead
authors.affiliation: Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
authors.forename: Danilo
authors.initials: D
authors.lastname: Casimiro
authors.affiliation: Columbia University, New York, New York.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Hammer For The Merck V/Hiv Vaccine Trials Network Study Team