Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.

Published

Journal Article

We used the simian immunodeficiency virus mac251 (SIV(mac251)) macaque model to study the effect of the dose of mucosal exposure on vaccine efficacy. We immunized macaques with a DNA prime followed by SIV gp120 protein immunization with ALVAC-SIV and gp120 in alum, and we challenged them with SIV(mac251) at either a single high dose or at two repeated low-dose exposures to a 10-fold-lower dose. Infection was neither prevented nor modified following a single high-dose challenge of the immunized macaques. However, two exposures to a 10-fold-lower dose resulted in protection from SIV(mac251) acquisition in 3 out of 12 macaques. The remaining animals that were infected had a modulated pathogenesis, significant downregulation of interferon responsive genes, and upregulation of genes involved in B- and T-cell responses. Thus, the choice of the experimental model greatly influences the vaccine efficacy of vaccines for human immunodeficiency virus (HIV).

Full Text

Duke Authors

Cited Authors

  • Vaccari, M; Keele, BF; Bosinger, SE; Doster, MN; Ma, Z-M; Pollara, J; Hryniewicz, A; Ferrari, G; Guan, Y; Forthal, DN; Venzon, D; Fenizia, C; Morgan, T; Montefiori, D; Lifson, JD; Miller, CJ; Silvestri, G; Rosati, M; Felber, BK; Pavlakis, GN; Tartaglia, J; Franchini, G

Published Date

  • March 2013

Published In

Volume / Issue

  • 87 / 6

Start / End Page

  • 3538 - 3548

PubMed ID

  • 23325681

Pubmed Central ID

  • 23325681

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

Digital Object Identifier (DOI)

  • 10.1128/JVI.02863-12

Language

  • eng

Conference Location

  • United States