Perspective abstract
Nature Medicine 14, 617 - 621 (2008)
Published online: 5 June 2008 | doi:10.1038/nm.f.1759
Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans
David I Watkins1, Dennis R Burton2, Esper G Kallas3, John P Moore4 & Wayne C Koff5
Abstract
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.
- David I. Watkins is at the Wisconsin National Primate Research Center, University of Wisconsin–Madison, 1220 Capitol Court, Madison, Wisconsin 53715, USA; he is also in the Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 6152 Medical Sciences Center, 1300 University Avenue, Madison, Wisconsin 53706, USA. e-mail: watkins@primate.wisc.edu
- Dennis R. Burton is in the Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
- Esper G. Kallas is in the Division of Clinical Immunology and Allergy, University of São Paulo, Laboratório de Investigação Médica 60, Av. Dr. Arnaldo 455, terceiro andar, São Paulo, SP, 01246-903, Brazil; he is also in the Division of Infectious Diseases, Federal University of São Paulo, Rua Mirassol 207, São Paulo, SP, 04044-010, Brazil.
- John P. Moore is in the Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Box 62, New York, New York 10021, USA.
- Wayne C. Koff is at the International AIDS Vaccine Initiative (IAVI), 110 William Street, 27th floor, New York, New York 10038, USA.
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