Core C - The University of Texas Medical Branch at Galveston

摘要 在导致人类疾病的病毒中，埃尼帕病毒、亨德拉病毒(HEV)和尼帕病毒(NIV)、 它们令人印象深刻的杀伤力脱颖而出。这些病毒是已知的最致命的人类病原体之一 NIV的病死率平均约为75%。值得注意的是，有证据表明有多轮 新城疫在人与人之间的传播。除了在澳大利亚和新城疫自然爆发的HEV外，主要是在 在印度和孟加拉国，有人担心HEV和NIV可能被用作生物恐怖主义的代理人。目前， 目前还没有被批准用于人类的埃尼帕病毒疫苗或治疗方法。因此，尼帕和 埃尼帕病毒病是世界卫生组织新研发项目上仅有的8种病原体之一 需要紧急研发行动的疫情威胁蓝图清单(http://www.who.int/blueprint/优先- 疾病/EN/)。CETR内的所有三个研究项目都侧重于开发广谱 针对HEV和NIV的疫苗或治疗药物。RP1使用基于HEV可溶性G(SG)的疫苗，即 目前在澳大利亚有马匹许可证。RP2专注于抗埃尼帕病毒的单抗，RP3 重点是减毒海尼帕病毒疫苗。CETR的一个独特之处在于，这些方法包括 最有希望的疫苗(HEV SG)和最有希望的抗病毒(人源单抗m102.4) 已经显示出有能力为非人类灵长类动物提供全面的预防和暴露后保护 (NHP)分别抗鸡细小病毒。CETR的所有三个研究项目和核心B都要求 应对措施需要在动物身上进行评估。联邦法律要求HEV和NIV在批准的 生物安全级别(BSL)-4级围堵实验室。核心C提供经批准的BSL-4设施和训练有素的 由经验丰富的BSL-4调查人员和工作人员组成的团队进行支持RP1-RP3和核心B的研究。 核心C将执行将进行的“有充分记录的”NHP功效研究和“关键的”NHP研究 符合基于GLP的质量协议，该协议将由专门的质量支持 保证/质量控制团队。Core C提供的服务将包括1)Well的安全存储库 BSL-4海尼帕病毒的特征种子库2)体外抗病毒活性测定；3)UTMB的采购 IACUC对动物方案的批准；3)动物的采购、住房和饲养；5)病毒挑战， 治疗和采集动物样本；6)进行临床研究的技术专长和设备 对样本进行病理和病毒学分析，并在BSL-4容器中进行尸检；7) 从感染埃尼帕病毒的动物身上收集的组织的组织病理学分析；以及8)质量体系 管理从NHP研究中收集的所有记录和数据。 相关性 BSL-4评估核心(核心C)为RP1、RP2、RP3和核心B提供BSL-4资源和专业知识。 核心C的目标是与研究项目负责人和工作人员、科学咨询委员会、 和NIAID/NIH，以推进针对HEV和NIV的对策的制定。

Abstract Among viruses that cause disease in humans the henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), stand out for their impressive lethality. These viruses are among the most deadly human pathogens known to man with case fatality rates averaging about 75% for NiV. Significantly, there is evidence of multiple rounds of person-to-person transmission of NiV. In addition to natural outbreaks of HeV in Australia and NiV primarily in India and Bangladesh, there is concern that HeV and NiV could be used as agents of bioterrorism. Currently, there are no henipavirus vaccines or treatments approved for human use. For these reasons Nipah and henipaviral diseases are one of only eight pathogens listed on the new World Health Organization R&D Blueprint list of epidemic threats needing urgent R&D action (http://www.who.int/blueprint/ priority- diseases/en/). All three of the Research Projects within the CETR focus on developing broad spectrum vaccines or therapeutics against HeV and NiV. RP1 employs a HeV soluble G (sG)-based vaccines that is currently licensed for horses in Australia. RP2 focuses on anti-henipavirus monoclonal antibodies, and RP3 focuses on attenuated henipavirus vaccines. A unique aspect of this CETR is that these approaches include the most promising vaccine (HeV sG) and the most promising antiviral (human monoclonal antibody m102.4) that have shown the ability to provide complete preventive and postexposure protection of nonhuman primates (NHPs) against henipaviruses, respectively. All three CETR Research Projects and Core B require that countermeasures be evaluated in animals. Federal law requires that HeV and NiV be handled in an approved Biosafety Level (BSL)-4 containment laboratory. Core C provides an approved BSL-4 facility and a trained and highly experienced team of BSL-4 investigators and staff to perform studies that support RP1-RP3 and Core B. Core C will perform “well-documented” NHP efficacy studies and “pivotal” NHP studies that will be conducted in accordance with a GLP-based quality agreement that will be supported by a dedicated quality assurance/quality control team. The services provided by Core C will include 1) a secure repository of well characterized seed stocks of BSL-4 henipaviruses 2) in vitro antiviral activity assays; 3) procurement of UTMB IACUC approval of animal protocols; 3) procurement, housing, and husbandry of animals; 5) virus challenge, treatment, and collection of samples from animals; 6) technical expertise and equipment to conduct clinical pathological and virological analysis of samples and to perform necropsies in BSL-4 containment; 7) histopathological analysis of tissues collected from animals infected with henipaviruses; and 8) quality systems management of all records and data collected from NHP studies. Relevance The BSL-4 Evaluation Core (Core C) provides BSL-4 resources and expertise for RP1, RP2, RP3, and Core B. The goal of Core C is to work closely with Research Project Leaders and staff, Scientific Advisory Committee, and NIAID/NIH to advance the development of countermeasures against HeV and NiV.