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

نویسندگان

  • Monica Vaccari
  • Brandon F Keele
  • Steven E Bosinger
  • Melvin N Doster
  • Zhong-Min Ma
  • Justin Pollara
  • Anna Hryniewicz
  • Guido Ferrari
  • Yongjun Guan
  • Donald N Forthal
  • David Venzon
  • Claudio Fenizia
  • Tia Morgan
  • David Montefiori
  • Jeffrey D Lifson
  • Chris J Miller
  • Guido Silvestri
  • Margherita Rosati
  • Barbara K Felber
  • George N Pavlakis
  • James Tartaglia
  • Genoveffa Franchini
چکیده

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).

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عنوان ژورنال:
  • Journal of virology

دوره 87 6  شماره 

صفحات  -

تاریخ انتشار 2013