Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers.
Development of a cytomegalovirus (CMV) vaccine is a priority. We evaluated a two component alphavirus replicon particle vaccine expressing CMV gB or a pp65/IE1 fusion protein, previously shown to induce robust antibody and cellular immune responses in mice, in a randomized, double-blind Phase 1 clinical trial in CMV seronegative subjects. Forty subjects received a lower dose (LD) or higher dose (HD) of vaccine or placebo by intramuscular or subcutaneous injection at Weeks 0, 8 and 24. The vaccine was well tolerated, with mild to moderate local reactogenicity, minimal systemic reactogenicity, and no clinically important changes in laboratory parameters. All vaccine recipients developed ex vivo, direct IFN-gamma ELISPOT responses to CMV antigens (maximal mean spot-forming cells per 10(6) PBMC in LD and HD groups of 348 and 504 for pp65, 83 and 113 for IE1, and 138 and 114 for gB), and neutralizing antibodies (maximal geometric mean titer 110 with LD and 218 with HD). Polyfunctional CD4(+) and CD8(+) T cell responses were detected by polychromatic flow cytometry. This alphavirus replicon particle vaccine was safe and induced neutralizing antibody and multifunctional T cell responses against three CMV antigens that are important targets for protective immunity.
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 44259, USA. David.Bernstein@cchmc.org
David I
DI
Bernstein
Elizabeth A
EA
Reap
Kevin
K
Katen
Aubrey
A
Watson
Kaitlin
K
Smith
Pamela
P
Norberg
Robert A
RA
Olmsted
Amy
A
Hoeper
John
J
Morris
Sarah
S
Negri
Maureen F
MF
Maughan
Jeffrey D
JD
Chulay
D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004311:Double-Blind Method; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D008875:Middle Aged; D008954:Models, Biological; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
D057134:Antibodies, Neutralizing; D000956:Antigens, Viral; D022482:Cytomegalovirus Vaccines