Zarling J M, Moran P A, Brewer L, Ashley R, Corey L
Oncogen, Seattle, Washington 98121.
J Virol. 1988 Dec;62(12):4481-5. doi: 10.1128/JVI.62.12.4481-4485.1988.
Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccines studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccines proliferated following stimulation with gD-2, whereas stimulation with gD-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine.
开展了多项研究,以确定用2型单纯疱疹病毒(HSV-2)糖蛋白亚单位疫苗对人类进行免疫是否会引发HSV特异性增殖细胞和细胞毒性T细胞的致敏。在所研究的所有8名接种疫苗者中,外周血淋巴细胞(PBL)在受到HSV-2、HSV-1和糖蛋白gB-1刺激后均通过增殖做出反应。这8名接种疫苗者中有5人的PBL在受到gD-2刺激后增殖,而受到gD-1刺激后增殖反应相对较低或无增殖反应。从3名对HSV-1和HSV-2表现出强烈增殖反应的接种疫苗者经HSV-2刺激的PBL中产生了T细胞克隆。在淋巴细胞增殖试验中研究的12个克隆中,发现9个对HSV-1和HSV-2具有交叉反应性。在所分离的约90个T细胞克隆中,14个表现出HSV特异性细胞毒性活性。放射免疫沉淀-聚丙烯酰胺凝胶电泳分析证实,这些接种疫苗者仅对HSV糖蛋白有抗体,而对亚单位疫苗中不存在的蛋白质没有抗体,这表明这些接种疫苗者未感染HSV。因此,用HSV-2糖蛋白亚单位疫苗对人类进行免疫会引发T细胞的致敏,这些T细胞在受到HSV及其糖蛋白刺激后会增殖,并且对HSV感染细胞具有细胞毒性活性。在用亚单位疫苗最后一次加强免疫后长达2年仍能检测到这种HSV特异性记忆T细胞。