title: Efficacy of multivalent adenovirus-based vaccine against simian immunodeficiency virus challenge.
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 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.
authors.affiliation: Department of Vaccines Basic Research, Merck Research Laboratories, Merck & Co., West Point, Pennsylvania 19486, USA. danilo_casimiro@merck.com
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Kara
authors.initials: K
authors.lastname: Cox
authors.forename: Aimin
authors.initials: A
authors.lastname: Tang
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Sykes
authors.forename: Meizhen
authors.initials: M
authors.lastname: Feng
authors.forename: Fubao
authors.initials: F
authors.lastname: Wang
authors.forename: Andrew
authors.initials: A
authors.lastname: Bett
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.forename: Jessica
authors.initials: J
authors.lastname: Flynn
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Tobery
authors.forename: Keith
authors.initials: K
authors.lastname: Wilson
authors.forename: Adam
authors.initials: A
authors.lastname: Finnefrock
authors.forename: Lingyi
authors.initials: L
authors.lastname: Huang
authors.forename: Salvatore
authors.initials: S
authors.lastname: Vitelli
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Deepa
authors.initials: D
authors.lastname: Patel
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Davies
authors.forename: Gwendolyn J
authors.initials: GJ
authors.lastname: Heidecker
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Freed
authors.forename: Sheri
authors.initials: S
authors.lastname: Dubey
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
mesh_terms: 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
chemical_list: D016915:AIDS Vaccines; D018449:SAIDS Vaccines; D014759:Viral Envelope Proteins