Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes
Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes
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DOI：
10.1038/415335a
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发表时间：
2002-01-17
期刊：
影响因子：
64.8
通讯作者：
Letvin, NL
中科院分区：
文献类型：
--
作者：
Barouch, DH;Kunstman, J;Letvin, NL
最近，候选艾滋病疫苗诱导的强大的病毒特异性细胞毒性T淋巴细胞(CTL)反应被证明可以控制病毒复制，防止病原性病毒攻击后猕猴的临床疾病进展(1-4)。在这里，我们表明，病毒逃避CTL识别可能导致这种部分免疫保护最终失败。先前已经在感染人类免疫缺陷病毒(HIV)的人(5-10)和感染猴免疫缺陷病毒(SIV)的猴子(11-13)中描述了逃脱CTL识别的病毒突变。在一组接种了致病混合猴-人免疫缺陷病毒(SHIV)的恒河猴中，CTL表位内病毒序列突变的频率与病毒复制水平相关。在血浆中检测不到病毒RNA的动物中，免疫优势的Gag CTL表位内的单核苷酸突变导致病毒逃避CTL，病毒突然复制，临床疾病进展，以及死于艾滋病相关并发症。这些数据表明，病毒逃避CTL识别可能是基于CTL的艾滋病疫苗的一个主要限制，这种疫苗可能在未来几年内被大量人类接种。
Potent virus-specific cytotoxic T lymphocyte (CTL) responses elicited by candidate AIDS vaccines have recently been shown to control viral replication and prevent clinical disease progression after pathogenic viral challenges in rhesus monkeys(1-4). Here we show that viral escape from CTL recognition can result in the eventual failure of this partial immune protection. Viral mutations that escape from CTL recognition have been previously described in humans infected with human immunodeficiency virus (HIV)(5-10) and monkeys infected with simian immunodeficiency virus (SIV)(11-13). In a cohort of rhesus monkeys that were vaccinated and subsequently infected with a pathogenic hybrid simian-human immunodeficiency virus (SHIV), the frequency of viral sequence mutations within CTL epitopes correlated with the level of viral replication. A single nucleotide mutation within an immunodominant Gag CTL epitope in an animal with undetectable plasma viral RNA resulted in viral escape from CTLs, a burst of viral replication, clinical disease progression, and death from AIDS-related complications. These data indicate that viral escape from CTL recognition may be a major limitation of the CTL-based AIDS vaccines that are likely to be administered to large human populations over the next several years.