Seth A, Ourmanov I, Kuroda M J, Schmitz J E, Carroll M W, Wyatt L S, Moss B, Forman M A, Hirsch V M, Letvin N L
Harvard Medical School, Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10112-6. doi: 10.1073/pnas.95.17.10112.
The utility of modified vaccinia virus Ankara (MVA) as a vector for eliciting AIDS virus-specific cytotoxic T lymphocytes (CTL) was explored in the simian immunodeficiency virus (SIV)/rhesus monkey model. After two intramuscular immunizations with recombinant MVA-SIVSM gag pol, the monkeys developed a Gag epitope-specific CTL response readily detected in peripheral blood lymphocytes by using a functional killing assay. Moreover, those immunizations also elicited a population of CD8+ T lymphocytes in the peripheral blood that bound a specific major histocompatibility complex class I/peptide tetramer. These Gag epitope-specific CD8+ T lymphocytes also were demonstrated by using both functional and tetramer-binding assays in lymph nodes of the immunized monkeys. These observations suggest that MVA may prove a useful vector for an HIV-1 vaccine. They also suggest that tetramer staining may be a useful technology for monitoring CTL generation in vaccine trials in nonhuman primates and in humans.
在猴免疫缺陷病毒（SIV）/恒河猴模型中，研究了改良安卡拉痘苗病毒（MVA）作为引发艾滋病病毒特异性细胞毒性T淋巴细胞（CTL）载体的效用。用重组MVA - SIVSM gag pol进行两次肌肉注射免疫后，通过功能杀伤试验在恒河猴外周血淋巴细胞中很容易检测到其产生的Gag表位特异性CTL反应。此外，这些免疫还在外周血中引发了一群与特定主要组织相容性复合体I类/肽四聚体结合的CD8 + T淋巴细胞。通过功能试验和四聚体结合试验在免疫猴的淋巴结中也证实了这些Gag表位特异性CD8 + T淋巴细胞。这些观察结果表明，MVA可能是一种用于HIV - 1疫苗的有用载体。它们还表明，四聚体染色可能是监测非人灵长类动物和人类疫苗试验中CTL产生的有用技术。
