Induction of protective immunity against herpes simplex virus with DNA encoding the immediate early protein ICP 27.
Induction of protective immunity against herpes simplex virus with DNA encoding the immediate early protein ICP 27.
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用编码立即早期蛋白 ICP 27 的 DNA 诱导针对单纯疱疹病毒的保护性免疫。
DOI：
10.1089/vim.1995.8.53
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Rouse,BT
中科院分区：
文献类型：
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作者：
Manickan,E;Yu,Z;Rouse,RJ;Wire,WS;Rouse,BT
使用在几个方面模拟人单纯疱疹病毒（HSV）感染的小鼠带状疱疹模型，评价编码立即早期蛋白ICP 27的质粒DNA作为疫苗的有效性。用DNA肌内免疫动物两次，然后用病毒攻击或杀死，并测量诱导的免疫应答的性质。肌肉注射编码ICP 27的质粒DNA（pc-ICP 27）后，70-80%的小鼠出现明显的固体保护，其余动物的病变延迟。从pc-ICP 27免疫小鼠获得的免疫脾细胞显示HSV特异性淋巴细胞增殖，MHC I类限制性细胞毒性T淋巴细胞（CTL）活性，和1型细胞因子的产生。这些动物还表现出迟发型超敏反应（DTH）。对同系裸小鼠进行的过继转移研究表明，免疫CD 4 +T细胞（而不是CD 8 +T细胞）的受体可以免受随后的HSV-1（菌株17）攻击。因此，pc-ICP 27 DNA免疫主要通过CD 4 +T细胞保护小鼠，并且这些细胞可能是Th-1型，因为在体外抗原刺激后仅检测到1型细胞因子。我们的研究结果表明编码非结构病毒蛋白的DNA作为抗HSV疫苗的潜在价值。
Using a mouse zosteriform model that mimics human herpes simplex virus (HSV) infection in several aspects, the effectiveness of plasmid DNA encoding the immediate early protein ICP 27 was evaluated as a vaccine. Animals were immunized intramuscularly twice with DNA, then either challenged with virus or killed, and the nature of the immune response induced was measured. After intramuscular injection with plasmid DNA encoding ICP 27 (pc-ICP 27), solid protection was evident in 70–80% of mice and the lesions were delayed in the remaining animals. Immune splenocytes obtained from pc-ICP 27 immune mice showed HSV-specific lymphoproliferation, MHC-class I restricted cytotoxic T-lymphocyte (CTL) activity, and type 1 cytokine production. These animals also exhibited delayed-type hypersensitivity (DTH) reactions. Adoptive transfer studies conducted on syngeneic nude mice revealed that those recipients of immune CD4+T cells, but not CD8+T cells, were protected from subsequent HSV-1 (strain 17) challenge. Thus pc-ICP 27 DNA immunization protected the mice principally by CD4+T cells and it is likely that these cells were Th-1 type because only type 1 cytokines were detectable after in vitro antigen stimulation. Our results indicate the potential value of DNA encoding nonstructural viral proteins as vaccines against HSV.