Rabies virus-based vaccines elicit neutralizing antibodies, poly-functional CD8⁺ T cell, and protect rhesus macaques from AIDS-like disease after SIV_mac251 challenge

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• 作者：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
• 关键词：Rabies virus ; HIV-1 ; Vaccine ; SIV_mac251 ; Rhabdovirus
• 刊名：Vaccine
• 出版年：2009
• 出版时间：11 December 2009
• 年：2009
• 卷：28
• 期：2
• 页码：299-308
• 全文大小：1750 K

文摘

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 TCID₅₀ 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.