Yasutomi Y, Palker T J, Gardner M B, Haynes B F, Letvin N L
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772.
J Immunol. 1993 Nov 1;151(9):5096-105.
In view of the importance of cell-associated virus in AIDS virus transmission, an HIV vaccine should be able to induce a virus-specific CTL response. Traditional subunit vaccines have not elicited virus-specific CD8+ MHC class I-restricted CTL. We have used the simian immunodeficiency virus of macaques (SIVmac)/rhesus monkey model to explore the use of CTL epitope peptide-helper peptide conjugates for the vaccine elicitation of AIDS virus-specific CTL. We found that both the CTL epitope peptide-helper peptide conjugate and the CTL epitope peptide alone, when delivered in an emulsion with IFA, induced CTL epitope-specific CD8+ MHC class I-restricted CTL. These effector cells recognized processed viral protein and were readily cloned from PBL of the immunized monkeys. Moreover, the cloned effector cells inhibited SIVmac replication in PBL. Immunization with the CTL epitope peptide used in this study also elicited a CD4+ PBL proliferative response, suggesting that the peptide also contained a helper epitope. These studies provide further evidence for the potential usefulness of peptide-based AIDS virus vaccines.
鉴于细胞相关病毒在艾滋病病毒传播中的重要性,一种HIV疫苗应能够诱导病毒特异性CTL反应。传统的亚单位疫苗尚未引发病毒特异性的CD8⁺MHC I类限制性CTL。我们利用猕猴猿猴免疫缺陷病毒(SIVmac)/恒河猴模型来探索使用CTL表位肽-辅助肽偶联物来引发艾滋病病毒特异性CTL的疫苗。我们发现,当与IFA一起以乳剂形式递送时,CTL表位肽-辅助肽偶联物和单独的CTL表位肽均可诱导CTL表位特异性的CD8⁺MHC I类限制性CTL。这些效应细胞识别加工后的病毒蛋白,并易于从免疫猴子的外周血淋巴细胞中克隆出来。此外,克隆的效应细胞抑制了SIVmac在PBL中的复制。用本研究中使用的CTL表位肽进行免疫也引发了CD4⁺PBL增殖反应,表明该肽还含有一个辅助表位。这些研究为基于肽的艾滋病病毒疫苗的潜在实用性提供了进一步的证据。