GENETIC VACCINES AND IMMUNITY TO HERPES SIMPLEX VIRUS

目前还没有针对许多病原体的有效疫苗， 单纯疱疹病毒（HSV）。 对于最佳的防御HSV，它可能是 最大化Th1的CD8+ T细胞和CD4+ T细胞应答所必需的 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（遗传）疫苗，通过以下途径给药， 最大程度地接合树突细胞系列的细胞。 最初使用于 体外系统，编码HSV全长蛋白的DNA构建体 或检测编码已知T和B细胞表位的小基因的 能够诱导诱导各种类型的免疫反应。 的 还将评估共刺激细胞因子环境的影响 关于诱导的应答的CD4+ Th1或Th2性质。 随后，发现构建物在体外充当有效的免疫原， 将以各种方式免疫小鼠。 递送系统将 包括转染树突细胞、脂质体以及微粒 用DNA包裹并通过基因枪注射 免疫接种 应对措施将从以下两个方面进行评估： 产生的免疫反应以及它们在 在HSV感染的小鼠模型中提供保护。 这些发现 应该与疫苗的未来发展有关， 成功控制HSV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.