Rabies virus-based vaccines elicit neutralizing antibodies, poly-functional CD8+ T cell, and protect rhesus macaques from AIDS-like disease after SIVmac251 challenge
Rabies virus-based vaccines elicit neutralizing antibodies, poly-functional CD8+ T cell, and protect rhesus macaques from AIDS-like disease after SIVmac251 challenge
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DOI：
10.1016/j.vaccine.2009.10.051
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发表时间：
2009-12-11
期刊：
影响因子：
5.5
通讯作者：
Schnell, Matthias J.
中科院分区：
文献类型：
--
作者：
Faul, Elizabeth J.;Aye, Pyone P.;Schnell, Matthias J.
评价高度减毒的狂犬病病毒（RV）疫苗载体针对高致病性SIVmac 251攻击的保护能力。将Mamu-A*01阴性恒河猴以四只一组用以下任一种免疫：表达SIVmac 239-GagPol的RV、表达SIVmac 239-Env的RV和表达SIVmac 239-GagPol的RV的组合，或用空RV载体。8周后，动物接受表达相同抗原的异源RV的加强免疫。在加强后12周，所有动物用100 TCID 50致病性SIVmac 251-CX静脉内攻击。与对照动物相比，两个疫苗组中的免疫猕猴的病毒设定点降低了1.3-1.6倍。GagPol/Env免疫的动物也具有显著较低的峰值病毒载量。与对照动物相比，接种疫苗的猕猴在攻击后更快地诱导SIVmac 251中和抗体和对各种SIV表位的CD 8（+）T细胞应答。此外，接种疫苗的猕猴更好地维持了外周记忆CD 4（+）T细胞，并能够在粘膜中建立多功能CD 8（+）T细胞反应。这些发现表明RV为基础的载体的承诺，并具有重要的意义，有效的艾滋病毒疫苗的发展。(C)2009爱思唯尔有限公司保留所有权利。
Highly attenuated rabies virus (RV) vaccine vectors were evaluated for their ability to protect against highly pathogenic SIVmac251 challenge. Mamu-A*01 negative rhesus macaques were immunized in groups of four with either: RV expressing SIVmac239-GagPol, a combination of RV expressing SIVmac239-Env and RV expressing SIVmac239-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 SIVmac251-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 SIVmac251 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. (C) 2009 Elsevier Ltd. All rights reserved.