Linhart H, Gundlach B R, Sopper S, Dittmer U, Mätz-Rensing K, Kuhn E M, Müller J, Hunsmann G, Stahl-Hennig C, Uberla K
Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg, Germany.
AIDS Res Hum Retroviruses. 1997 May 1;13(7):593-9. doi: 10.1089/aid.1997.13.593.
Live attenuated simian immunodeficiency virus (SIV) vaccines, like nef deletion mutants, have been the most effective vaccines tested in the SIV/macaque model so far. The efficacy of live attenuated SIV vaccines in therapeutic vaccination and postexposure prophylaxis has not been determined. Inoculation of macaques with a pathogenic challenge virus and an attenuated SIV vaccine at the same time mimics postexposure vaccination, whereby vaccination with the attenuated virus is performed as rapidly as possible after exposure to pathogenic SIV. In the study presented here, four rhesus macaques were coinfected with pathogenic SIV and a nearly 3000-fold excess of a nef deletion mutant of SIV. Four macaques received pathogenic SIV and an approximately 200-fold excess of a nef deletion mutant expressing interleukin 2 (IL-2). The IL-2-expressing SIV had been previously constructed to enhance the immunogenicity of live attenuated SIV vaccines. All coinfected macaques had a high viral load, and some of them developed AIDS-like symptoms and pathological alterations rapidly. In the presence of pathogenic SIV, both live attenuated SIV vaccines did not protect from disease in this postexposure vaccination model.
减毒活猴免疫缺陷病毒（SIV）疫苗，如nef缺失突变体，是迄今为止在SIV/猕猴模型中测试过的最有效的疫苗。减毒活SIV疫苗在治疗性疫苗接种和暴露后预防中的效果尚未确定。同时用致病性攻击病毒和减毒SIV疫苗接种猕猴模拟暴露后接种，即在暴露于致病性SIV后尽快用减毒病毒进行接种。在本研究中，4只恒河猴同时感染了致病性SIV和近3000倍过量的SIV nef缺失突变体。4只猕猴接受了致病性SIV和大约200倍过量的表达白细胞介素2（IL-2）的nef缺失突变体。先前构建表达IL-2的SIV是为了增强减毒活SIV疫苗的免疫原性。所有同时感染的猕猴都有高病毒载量，其中一些迅速出现了类似艾滋病的症状和病理改变。在致病性SIV存在的情况下，在这个暴露后接种疫苗模型中，两种减毒活SIV疫苗都不能预防疾病。
