Core B: Animal Studies

摘要 P01的总体目标是开发一种能够保护婴儿和儿童免受 呼吸道合胞病毒病，包括在棉鼠身上有效测试该疫苗所需的工具 最终在婴儿和儿童身上也是如此。核心B(动物模型使用和开发核心)支持 本项目资助范围内棉花大鼠模型的研制和使用(P0.01)。引路人 动物模型的核心原则是有效地规划和利用动物，标准化 对活体数据的处理、服务的可靠性和一致性的评估，从而作为集成的平台 P01中的数据。核心内提供的基本专业知识是实验动物医学和 临床和解剖病理学。核心中心设在兽医部，并进行协调 生物科学。Stefan Niewiesk博士，被提名为核心主任，一直致力于治疗呼吸道病毒感染 在过去的15年里，棉花鼠一直是P01的主要调查人员的积极合作者。他是 兽医微生物学证书(德国委员会)和欧洲实验室学院文凭 动物医学。克里斯塔·拉·佩尔博士(合作研究员)，美国大学 兽医病理学和与Niewiesk博士在棉鼠病理学方面的合作，将提供病理学 对核心的评估。在项目1-3(Teng博士、Peeples博士、Li博士)中，一种基因工程RSV 通过在NS-1蛋白G中引入突变将产生致病性和增强的免疫原性 蛋白质和聚合酶。在项目4(Mejias博士)中，基因表达特征和抗体反应 将对患有轻度和重度疾病的儿童进行检测，并将其与棉鼠对 接种疫苗。核心B开发了支持各种项目所需的分析和试剂，以及 将患者定义的免疫标志物翻译回棉鼠模型以改进对 候选疫苗。

Abstract The overall goal of this P01 is to develop an attenuated vaccine capable of protecting infants and children from respiratory syncytial virus disease, including the tools necessary to test this vaccine effectively in cotton rats and eventually in infants and children. Core B (Animal Model Use and Development Core) supports the development and use of the cotton rat model utilized within this Program Project Grant (P01). The guiding principals for the animal model core are efficient planning and utilization of animals, standardization of processing, reliability of service and consistent evaluation of in vivo data thus serving as a platform to integrate data across the P01. The fundamental expertise provided within the core is laboratory animal medicine and clinical and anatomic pathology. The Core is housed and coordinated in the Department of Veterinary Biosciences. Dr. Stefan Niewiesk, proposed Core Director has been working with viral respiratory infections in cotton rats for the last 15 years and is an active collaborator with the principal investigators for the P01. He is certified in Veterinary Microbiology (German boards) and a diplomate of the European College of Laboratory Animal Medicine. Dr. Krista La Perle (co-investigator), who is a diplomate of the American College of Veterinary Pathology and has worked with Dr. Niewiesk on cotton rat pathology, will provide pathological evaluations for the Core. In Projects 1-3 (Drs. Teng, Peeples, Li), a genetically engineered RSV with reduced pathogenicity and increased immunogenicity will be generated by introducing mutations in the NS-1 protein, G protein, and the polymerase. In Project 4 (Dr. Mejias), the gene expression signature and antibody response of children with mild and severe disease will be determined and compared to the response of cotton rats to vaccination. Core B has developed assays and reagents necessary to support the various projects, and translate markers of immunity defined in patients back to the cotton rat model to improve the evaluation of vaccine candidates.