MUCOSAL IMMUNITY IN CONTROL OF HERPETIC INFECTION

这项建议的目的是评估重组人的能力 表达单纯疱疹病毒基因的减毒沙门氏菌 诱导动物模型对病毒攻击的保护性免疫 系统。载体系统，虽然通过口服途径给药，但 预计会诱导保护性水平的抗体，也许还有细胞 远离免疫部位粘膜部位的介导性免疫 此外，还应诱导系统免疫的保护性水平。 粘膜部位的有效免疫可能有助于预防感染，以及 抗疱疹病毒疫苗的重要目标是感染 总是伴随着潜伏期和复发的可能性 疾病。为了测试粘膜免疫的有效性，小鼠将 通过呼吸道和阴道途径受到挑战。系统免疫 将通过控制随后的带状病毒传播进行评估 在通过真皮感染之后。各种沙门氏菌载体 以不同方式表达HSV基因将被评估为疫苗和 将对体液和T细胞的程度进行测量 介导粘膜部位、血清和淋巴组织的免疫反应。 将为体外参数之间的相关性寻找证据 免疫和随后对病毒攻击的反应在不同的 模特们。特别强调的是细胞毒性T淋巴细胞 反应，因为假设对HSV的固体免疫力 免疫反应中必须包括免疫形式。我们的研究 将评估重组减毒沙门氏菌载体系统是否有效 承诺作为人类预防单纯疱疹病毒疫苗的一种手段。

The aim of this proposal is to evaluate the ability of recombinant attenuated Salmonella that express genes of Herpes simplex virus (HSV) to induce protective immunity against viral challenge in animal model systems. The vector system, although administered via the oral route, is expected to induce protective levels of antibody and perhaps cell mediated immunity at mucosal sites distant from the site of immunization and, in addition, should induce protective levels of systemic immunity. Effective immunity at mucosal sites may serve to prevent infection, an important objective for antiherpesvirus vaccines since infection is invariably followed by latency and the likelihood of recrudescent disease. To test the effectiveness of mucosal immunity, mice will be challenged via the respiratory and vaginal routes. Systemic immunity will be evaluated by control of subsequent zosteriform spread of virus following infection via the dermis. Various Salmonella vectors expressing HSV genes in different ways will be evaluated as vaccines and measurements will be made of the extent of the humoral and T cell mediated immune responses at mucosal sites, serum and lymphoid tissues. Evidence will be sought for correlations between in vitro parameters of immunity and the subsequent response to viral challenge in the different models. Especial emphasis will be directed at the cytotoxic T lymphocyte responses since it is hypothesized that for solid immunity to HSV this form of immunity must be included in the immune response. Our research will evaluate if a recombinant attenuated Salmonella vector system holds promise as a means of vaccinating against HSV in man.