Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans.
The adenovirus type 5 (Ad5)-based vaccine developed by Merck failed to either prevent HIV-1 infection or suppress viral load in subsequently infected subjects in the STEP human Phase 2b efficacy trial. Analogous vaccines had previously also failed in the simian immunodeficiency virus (SIV) challenge-rhesus macaque model. In contrast, vaccine protection studies that used challenge with a chimeric simian-human immunodeficiency virus (SHIV89.6P) in macaques did not predict the human trial results. Ad5 vector-based vaccines did not protect macaques from infection after SHIV89.6P challenge but did cause a substantial reduction in viral load and a preservation of CD4+ T cell counts after infection, findings that were not reproduced in the human trials. Although the SIV challenge model is incompletely validated, we propose that its expanded use can help facilitate the prioritization of candidate HIV-1 vaccines, ensuring that resources are focused on the most promising candidates. Vaccine designers must now develop T cell vaccine strategies that reduce viral load after heterologous challenge.
Watkins
David I
DI
Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1220 Capitol Court, Madison, Wisconsin 53715, USA. watkins@primate.wisc.edu
Burton
Dennis R
DR
Kallas
Esper G
EG
Moore
John P
JP
Koff
Wayne C
WC
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D017322:Clinical Trials, Phase II as Topic; D004195:Disease Models, Animal; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008253:Macaca mulatta; D017211:Treatment Failure; D019562:Viral Load / Q000379:methods; D014779:Virus Replication / Q000276:immunology / Q000502:physiology
D016915:AIDS Vaccines