Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans

David I. Watkins, Dennis R. Burton, Esper G. Kallas, John P. Moore, Wayne C. Koff

Research output: Contribution to journalReview article

212 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)617-621
Number of pages5
JournalNature medicine
Volume14
Issue number6
DOIs
StatePublished - Jun 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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