Efficacy of multivalent adenovirus-based vaccine against simian immunodeficiency virus challenge.
The prophylactic efficacies of several multivalent replication-incompetent adenovirus serotype 5 (Ad5) vaccines were examined in rhesus macaques using an intrarectal high-dose simian immunodeficiency virus SIVmac239 challenge model. Cohorts of Mamu-A*01(+)/B*17(-) Indian rhesus macaques were immunized with one of several combinations of Ad5 vectors expressing Gag, Pol, Nef, and Env gp140; for comparison, a Mamu-A*01(+) cohort was immunized using the Ad5 vector alone. There was no sign of immunological interference between antigens in the immunized animals. In general, expansion of the antigen breadth resulted in more favorable virological outcomes. In particular, the order of efficacy trended as follows: Gag/Pol/Nef/Env approximately Gag/Pol > Gag approximately Gag/Pol/Nef > Nef. However, the precision in ranking the vaccines based on the study results may be limited by the cohort size, and as such, may warrant additional testing. The implications of these results in light of the recent discouraging results of the phase IIb study of the trivalent Ad5 HIV-1 vaccine are discussed.
Casimiro
Danilo R
DR
Department of Vaccines Basic Research, Merck Research Laboratories, Merck & Co., West Point, Pennsylvania 19486, USA. danilo_casimiro@merck.com
Cox
Kara
K
Tang
Aimin
A
Sykes
Kara J
KJ
Feng
Meizhen
M
Wang
Fubao
F
Bett
Andrew
A
Schleif
William A
WA
Liang
Xiaoping
X
Flynn
Jessica
J
Tobery
Timothy W
TW
Wilson
Keith
K
Finnefrock
Adam
A
Huang
Lingyi
L
Vitelli
Salvatore
S
Lin
Jing
J
Patel
Deepa
D
Davies
Mary-Ellen
ME
Heidecker
Gwendolyn J
GJ
Freed
Daniel C
DC
Dubey
Sheri
S
O'Connor
David H
DH
Watkins
David I
DI
Zhang
Zhi-Qiang
ZQ
Shiver
John W
JW
D016915:AIDS Vaccines / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000276:immunology
D016915:AIDS Vaccines; D018449:SAIDS Vaccines; D014759:Viral Envelope Proteins