MUCOSAL IMMUNITY IN CONTROL OF HERPETIC INFECTION

该提案的目的是评估重组的能力， 表达单纯疱疹病毒（HSV）基因的减毒沙门氏菌， 诱导抗病毒攻击保护性免疫动物模型 系统. 载体系统，虽然通过口服途径给药， 预期诱导抗体的保护水平， 在远离免疫部位的粘膜部位介导免疫 此外，还应诱导保护性水平的全身免疫。 粘膜部位的有效免疫可用于预防感染， 抗疱疹病毒疫苗重要目的是因为感染 不可避免的是潜伏期和复发的可能性 疾病 为了测试粘膜免疫的有效性，将小鼠 通过呼吸道和阴道感染 全身免疫 将通过控制随后带状疱疹病毒传播进行评价 感染后通过真皮。 各种沙门氏菌载体 将以不同方式表达HSV基因作为疫苗进行评价， 将测量体液和T细胞的程度， 介导粘膜部位、血清和淋巴组织的免疫应答。 将寻找体外参数之间相关性的证据， 免疫力和随后对病毒攻击的反应， 模型 特别强调的是细胞毒性T淋巴细胞 因为假设对于HSV的固体免疫， 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 承诺作为一种手段接种抗HSV的人。

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.