IN VIVO ANIMAL MODEL EVALUATION OF CANDIDATE VACCINES

本项目所做的研究将仔细地将调查结果相互交叉 将项目1和项目2中的每一个引入到适当的动物模型系统中，以测试候选物 疫苗株。 目标如下： 首先，将测试来自项目1的基因工程突变体， 最初在小鼠中，随后在豚鼠中，以确定它们的 在中枢神经系统、外周组织中复制的能力，以建立潜伏期， 在豚鼠中引起复发性病变，在消退后重新激活 保护这些动物物种免受 毒性病毒 这些研究将有助于原型的设计 根据项目1和项目3的研究结果， 第二，一旦候选疫苗株被确定， 小鼠和豚鼠的攻击研究将使用不同的 免疫途径和攻毒途径。 成功的挑战将进一步 与全身和粘膜免疫反应相关。 第三，尝试通过新的和新的免疫增强系统和粘膜免疫。 在可行性实验中谨慎使用白细胞介素， 启动。 这些实验将利用IL-4、IL-5和/或IL-6， 免疫，以确定其对免疫应答的影响。 如果豁免权可以 在没有不利影响证据的情况下，将尝试 评估在各种启动子下携带IL基因的重组病毒。 从这些研究中获得的知识将为更多的研究提供基础。 详细的动物安全性和免疫原性研究，预期人体 审判

The studies done in this Project will carefully interdigitate the findings of Projects 1 and 2 into appropriate animal model systems to test candidate vaccine strains. The objectives are as follows: First, genetically engineered mutants from Project 1 will be tested initially in mice and subsequently in guinea pigs to determine their capacity to replicate in the CNS, peripheral tissue, to establish latency, to cause recurrent lesions in guinea pigs, to reactivate upon explantation from ganglia, and to protect these animal species from challenge with virulent viruses. These studies will aid in the design of prototype vaccines strains based on the results of studies in Projects 1 and 3. Second, once candidate vaccine strains become identified, extensive challenge studies in mice and guinea pigs will be done utilizing different routes of immunization and challenge. Successful challenge will be further correlated with systemic and mucosal immune responses. Third, attempts to enhance systemic and mucosal immunity by novel and careful employment of interleukins in feasibility experiments will be initiated. These experiments will utilize IL-4, IL-5, and/or IL-6 before immunization to determine its effects on immune response. If immunity can be enhanced without evidence of adverse effects, an attempt will be made to evaluate recombinant viruses carrying IL genes under various promoters. The knowledge gained from these studies will provide a basis for more detailed animal safety and immunogenicity studies in anticipation of human trials.