Rabies virus-based vaccines elicit neutralizing antibodies, poly-functional CD8+ T cell, and protect rhesus macaques from AIDS-like disease after SIV(mac251) challenge.

Published

Journal Article

Highly attenuated rabies virus (RV) vaccine vectors were evaluated for their ability to protect against highly pathogenic SIV(mac251) challenge. Mamu-A*01 negative rhesus macaques were immunized in groups of four with either: RV expressing SIV(mac239)-GagPol, a combination of RV expressing SIV(mac239)-Env and RV expressing SIV(mac239)-GagPol, or with empty RV vectors. Eight weeks later animals received a booster immunization with a heterologous RV expressing the same antigens. At 12 weeks post-boost, all animals were challenged intravenously with 100 TCID(50) of pathogenic SIV(mac251-CX). Immunized macaques in both vaccine groups had 1.3-1.6-log-fold decrease in viral set point compared to control animals. The GagPol/Env immunized animals also had a significantly lower peak viral load. When compared to control animals following challenge, vaccinated macaques had a more rapid induction of SIV(mac251) neutralizing antibodies and of CD8(+) T cell responses to various SIV epitopes. Moreover, vaccinated macaques better maintained peripheral memory CD4(+) T cells and were able to mount a poly-functional CD8(+) T cell response in the mucosa. These findings indicate promise for RV-based vectors and have important implications for the development of an efficacious HIV vaccine.

Full Text

Duke Authors

Cited Authors

  • Faul, EJ; Aye, PP; Papaneri, AB; Pahar, B; McGettigan, JP; Schiro, F; Chervoneva, I; Montefiori, DC; Lackner, AA; Schnell, MJ

Published Date

  • December 11, 2009

Published In

Volume / Issue

  • 28 / 2

Start / End Page

  • 299 - 308

PubMed ID

  • 19879223

Pubmed Central ID

  • 19879223

Electronic International Standard Serial Number (EISSN)

  • 1873-2518

Digital Object Identifier (DOI)

  • 10.1016/j.vaccine.2009.10.051

Language

  • eng

Conference Location

  • Netherlands