Barouch Dan H, Kunstman Jennifer, Kuroda Marcelo J, Schmitz Jörn E, Santra Sampa, Peyerl Fred W, Krivulka Georgia R, Beaudry Kristin, Lifton Michelle A, Gorgone Darci A, Montefiori David C, Lewis Mark G, Wolinsky Steven M, Letvin Norman L
Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
Nature. 2002 Jan 17;415(6869):335-9. doi: 10.1038/415335a.
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. 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) and monkeys infected with simian immunodeficiency virus (SIV). 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.
最近的研究表明，候选艾滋病疫苗引发的强效病毒特异性细胞毒性T淋巴细胞（CTL）反应能够控制病毒复制，并在恒河猴受到致病性病毒攻击后预防临床疾病进展。在此，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效。先前在感染人类免疫缺陷病毒（HIV）的人类和感染猿猴免疫缺陷病毒（SIV）的猴子中，已发现逃避CTL识别的病毒突变。在一组接种疫苗后感染致病性杂交猿猴-人类免疫缺陷病毒（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。在一只血浆病毒RNA检测不到的动物中，免疫显性Gag CTL表位内的一个单核苷酸突变导致病毒逃避CTL，引发病毒复制爆发、临床疾病进展，并死于艾滋病相关并发症。这些数据表明，病毒逃避CTL识别可能是未来几年可能用于大量人群的基于CTL的艾滋病疫苗的一个主要限制。
