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Efficacy of multivalent adenovirus-based vaccine against simian immunodeficiency virus challenge. 2010
Danilo R Casimiro, and
Kara Cox, and
Aimin Tang, and
Kara J Sykes, and
Meizhen Feng, and
Fubao Wang, and
Andrew Bett, and
William A Schleif, and
Xiaoping Liang, and
Jessica Flynn, and
Timothy W Tobery, and
Keith Wilson, and
Adam Finnefrock, and
Lingyi Huang, and
Salvatore Vitelli, and
Jing Lin, and
Deepa Patel, and
Mary-Ellen Davies, and
Gwendolyn J Heidecker, and
Daniel C Freed, and
Sheri Dubey, and
David H O'Connor, and
David I Watkins, and
Zhi-Qiang Zhang, and
John W Shiver
Department of Vaccines Basic Research, Merck Research Laboratories, Merck & Co., West Point, Pennsylvania 19486, USA. danilo_casimiro@merck.com
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.
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Xiaoping Liang, and
Jessica Flynn, and
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Keith Wilson, and
Adam Finnefrock, and
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Jing Lin, and
Deepa Patel, and
Mary-Ellen Davies, and
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