Efficacy of multivalent adenovirus-based vaccine against simian immunodeficiency virus challenge

Danilo R. Casimiro, Kara Cox, Aimin Tang, Kara J. Sykes, Meizhen Feng, Fubao Wang, Andrew Bett, William A. Schleif, Xiaoping Liang, Jessica Flynn, Timothy W. Tobery, Keith Wilson, Adam Finnefrock, Lingyi Huang, Salvatore Vitelli, Jing Lin, Deepa Patel, Mary Ellen Davies, Gwendolyn J. Heidecker, Daniel C. FreedSheri Dubey, David H. O'Connor, David I. Watkins, Zhi Qiang Zhang, John W. Shiver

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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 ≈ Gag/Pol > Gag ≈ 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.

Original languageEnglish (US)
Pages (from-to)2996-3003
Number of pages8
JournalJournal of virology
Volume84
Issue number6
DOIs
StatePublished - Mar 2010
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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