Shen L, Chen Z W, Miller M D, Stallard V, Mazzara G P, Panicali D L, Letvin N L
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772.
Science. 1991 Apr 19;252(5004):440-3. doi: 10.1126/science.1708168.
Evidence indicates that cytotoxic T lymphocytes (CTLs) may be important in containing the spread of the human immunodeficiency virus (HIV) in the infected host. Although the use of recombinant viruses has been proposed as an approach to elicit protective immunity against HIV, the ability of recombinant viral constructs to elicit CD8+ CTL responses in higher primates has never been demonstrated. A live recombinant virus, vaccinia-simian immunodeficiency virus of macaques (SIVmac), was used to determine whether such a genetically restricted, T lymphocyte-mediated antiviral response could be generated in a primate. Vaccinia-SIVmac vaccination elicited an SIVmac Gag-specific, CD8+ CTL response in rhesus monkeys. These CTLs recognized a peptide fragment that spans residues 171 to 195 of the Gag protein. The rhesus monkey major histocompatibility complex (MHC) class I gene product restricting this CTL response was defined. Both the vaccinated and SIVmac-infected monkeys that shared this MHC class I gene product developed CTLs with the same Gag epitope specificity. These findings support the use of recombinant virus vaccines for the prevention of HIV infections in humans.
有证据表明，细胞毒性T淋巴细胞（CTLs）在抑制人类免疫缺陷病毒（HIV）在受感染宿主中的传播方面可能很重要。尽管有人提出使用重组病毒作为引发针对HIV的保护性免疫的一种方法，但重组病毒构建体在高等灵长类动物中引发CD8 + CTL反应的能力从未得到证实。一种活重组病毒，猕猴痘苗-猴免疫缺陷病毒（SIVmac），被用于确定在灵长类动物中是否可以产生这种基因限制的、T淋巴细胞介导的抗病毒反应。痘苗-SIVmac疫苗接种在恒河猴中引发了SIVmac Gag特异性的CD8 + CTL反应。这些CTL识别跨越Gag蛋白第171至195位残基的肽片段。确定了限制这种CTL反应的恒河猴主要组织相容性复合体（MHC）I类基因产物。共享这种MHC I类基因产物的接种疫苗和感染SIVmac的猴子都产生了具有相同Gag表位特异性的CTL。这些发现支持使用重组病毒疫苗预防人类HIV感染。
