Highly attenuated rabies virus-based vaccine vectors expressing simian-human immunodeficiency virus89.6P Env and simian immunodeficiency virusmac239 Gag are safe in rhesus macaques and protect from an AIDS-like disease
Highly attenuated rabies virus-based vaccine vectors expressing simian-human immunodeficiency virus89.6P Env and simian immunodeficiency virusmac239 Gag are safe in rhesus macaques and protect from an AIDS-like disease
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DOI：
10.1086/512243
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发表时间：
2007-04-01
影响因子：
6.4
通讯作者：
Schnell, Matthias J.
中科院分区：
文献类型：
--
作者：
McKenna, Philip M.;Koser, Martin L.;Schnell, Matthias J.
我们分析了表达猴-人免疫缺陷病毒（SHIV）-1（89.6P）Env或猴免疫缺陷病毒（SIV）（mac 239）Gag的减毒狂犬病病毒载体在恒河猴中的安全性和免疫原性。用两种疫苗构建体免疫4只试验猕猴，2只对照猕猴接受空狂犬病载体。在初次免疫后检测到针对狂犬病病毒糖蛋白（G）和SHIV89.6P Env的血清转化，但未观察到针对SHIV抗原的细胞应答。HIV/SIV特异性免疫应答并没有通过使用相同载体的加强而增强。因此，我们构建了表达SHIV 89.6P Env和SIV mac 239 Gag的载体，其中狂犬病G被水泡性口炎病毒（VSV）的G蛋白取代。初次免疫后两年，用狂犬病病毒-VSV G载体加强免疫导致SIV/HIV特异性免疫应答。在用SHIV89.6P攻击后，试验猕猴控制了感染，而对照猕猴具有高水平的病毒血症和CD 4（+）T细胞的严重损失，其中1只对照猕猴死于艾滋病样疾病。
We analyzed the safety and immunogenicity of attenuated rabies virus vectors expressing simian-human immunodeficiency virus (SHIV)-1(89.6P) Env or simian immunodeficiency virus (SIV)(mac239) Gag in rhesus macaques. Four test macaques were immunized with both vaccine constructs, and 2 control macaques received an empty rabies vector. Seroconversion against rabies virus glycoprotein (G) and SHIV89.6P Env was detected after the initial immunization, but no cellular responses against SHIV antigens were observed. HIV/SIV-specific immune responses were not enhanced by boosts with the same vectors. Therefore, we constructed vectors expressing SHIV89.6P Env and SIV mac239 Gag in which the rabies G was replaced with the G protein of vesicular stomatitis virus (VSV). Two years after initial immunization, a boost with the rabies-VSV G vectors resulted in SIV/HIV-specific immune responses. Upon challenge with SHIV89.6P test macaques controlled the infection, whereas control macaques had high levels of viremia and a profound loss of CD4(+) T cells, with 1 control macaque dying of an AIDS-like disease.