Safety and Immunogenicity of the MRKAd5 gag HIV Type 1 Vaccine in a Worldwide Phase 1 Study of Healthy Adults.
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.
Nicholson
Ouzama
O
Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
DiCandilo
Fay
F
Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
Kublin
James
J
Fred Hutchinson Cancer Research Center, Seattle, Washington.
Sun
Xiao
X
Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
Quirk
Erin
E
Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
Miller
Michelle
M
Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
Gray
Glenda
G
University of Witwatersrand, Johannesburg, South Africa.
Pape
Jean
J
Weill Cornell Medical College, New York, New York.
Robertson
Michael N
MN
Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
Mehrotra
Devan V
DV
Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
Self
Steven
S
Fred Hutchinson Cancer Research Center, Seattle, Washington.
Turner
Katherine
K
Fred Hutchinson Cancer Research Center, Seattle, Washington.
Sanchez
Jorge
J
Asociacion Civil Impacta Salud y Educacion, Lima, Peru and Investigaciones Medicas en Salu, Immensa, Lima, Peru.
Pitisuttithum
Punnee
P
Mahidol University, Bangkok, Thailand.
Duerr
Ann
A
Fred Hutchinson Cancer Research Center, Seattle, Washington.|University of Washington, Seattle, Washington.
Dubey
Sheri
S
Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
Kierstead
Lisa
L
Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
Casimiro
Danilo
D
Merck & Co., Inc., North Wales, Pennsylvania; current affiliation: GSK Biologicals, King of Prussia, Pennsylvania.
Hammer For The Merck V/Hiv Vaccine Trials Network Study Team
Scott M
SM
Columbia University, New York, New York.