GENETIC VACCINES AND IMMUNITY TO HERPES SIMPLEX VIRUS

目前还没有有效的疫苗可用于许多制剂，包括 单纯疱疹病毒(HSV)。为了对HSV进行最佳防御，可能是 最大化Th1的CD8+T细胞和CD4+T细胞反应所必需的 亚型，因为这些免疫成分对于迅速和 有效清除病毒。诱导这种反应可以通过以下方式实现 适当设计的DNA(基因)疫苗通过下列途径接种 最大限度地接触树突状细胞系列的细胞。最初在中使用 体外系统，编码HSV全长蛋白的DNA构建 或编码已知T和B细胞表位的微型基因将被测试其 能够诱导各种类型的免疫反应。这个 还将评估共刺激细胞因子环境的影响。 至于CD4+Th1或Th2诱导的反应性质。 随后，在体外发现了作为有效免疫原的构建物 将被用来以各种方式免疫小鼠。交付系统将 包括转染树突状细胞、脂质体以及微粒 包裹着DNA并通过基因枪给药。免疫接种 将从以下两个方面对答复进行评估： 产生的免疫反应以及它们在 对单纯疱疹病毒感染小鼠模型的保护作用。调查结果 应该与疫苗的未来发展相关， 成功控制单纯疱疹病毒感染。

Effective vaccines are not currently available for many agents including herpes simplex virus (HSV). For optimal defense against HSV it may be necessary to maximize CD8+ T cell and CD4+ T cell responses of the Th1 subtype, since these components of immunity are crucial for prompt and effective viral clearance. Inducing such responses could be achieved by appropriately designed DNA (genetic) vaccines administered by routes which maximally engage cells of the dendritic cell series. Initially using in vitro systems, DNA constructs encoding either full length proteins of HSV or minigenes encoding known T and B cell epitopes will be tested for their ability to induce various types of immune responses induced. The influence of the costimulatory cytokine environment will also be evaluated as regards the CD4+ Th1 or Th2 nature of the response induced. Subsequently, constructions found to act as effective immunogens in vitro will be used to immunize mice in various ways. Delivery systems will include transfected dendritic cells, liposomes, as well as microparticles encoated with DNA and administered via a gene gun. Immunizations responses will be evaluated both in terms of the type and magnitude of immune responses generated as well as for their effectiveness at conferring protection in mouse models of HSV infection. The findings should be relevant to the future development of vaccines that will successfully control HSV infections.