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

Authors

• Elizabeth J Faul
• Pyone P Aye
• Amy B Papaneri
• Bapi Pahar
• James P McGettigan
• Faith Schiro
• Inna Chervoneva
• David C Montefiori
• Andrew A Lackner
• Matthias J Schnell

Publication/Presentation Date

12-11-2009

Abstract

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.

Volume

28

Issue

2

First Page

299

Last Page

308

ISSN

1873-2518

Published In/Presented At

Faul, E. J., Aye, P. P., Papaneri, A. B., Pahar, B., McGettigan, J. P., Schiro, F., Chervoneva, I., Montefiori, D. C., Lackner, A. A., & Schnell, M. J. (2009). Rabies virus-based vaccines elicit neutralizing antibodies, poly-functional CD8+ T cell, and protect rhesus macaques from AIDS-like disease after SIV(mac251) challenge. Vaccine, 28(2), 299–308. https://doi.org/10.1016/j.vaccine.2009.10.051

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

19879223

Department(s)

Administration and Leadership

Document Type

Article