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

Autor: Zhong-Min Ma, Steven E. Bosinger, Tia Morgan, David Venzon, Melvin N. Doster, Christopher J. Miller, Barbara K. Felber, James Tartaglia, David C. Montefiori, Margherita Rosati, Justin Pollara, George N. Pavlakis, Monica Vaccari, Donald N. Forthal, Guido Ferrari, Claudio Fenizia, Genoveffa Franchini, Brandon F. Keele, Yongjun Guan, Jeffrey D. Lifson, Guido Silvestri, Anna Hryniewicz
Rok vydání: 2013
Předmět:
Zdroj: Journal of virology. 87(6)
ISSN: 1098-5514
Popis: 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).
Databáze: OpenAIRE