BSL-4 Evaluation Core (Core B)

项目摘要/摘要-BSL-4评估核心(核心B) 在导致人类疾病的病毒中，丝状病毒、埃博拉病毒和马尔堡病毒因其 杀伤力令人印象深刻。这些病毒是报告病例患者已知的最致命的人类病原体。 死亡率高达90%。最近在西非史无前例的2013-16年扎伊尔埃博拉病毒疫情 导致超过28,000例病例和11,000人死亡表明丝状病毒能够在新的 地区。除了自然暴发，埃博拉病毒和马尔堡病毒也是已知的 以前的生物武器计划，并有可能被故意滥用。目前，还没有丝状病毒 批准人类使用的疫苗或治疗方法。由于这些原因，埃博拉病毒和马尔堡病毒最近 被列为新的美国卫生与公众服务部11种人类病原体中的仅2种 (HHS)A类精选代理的第1级列表。该中心内的所有三个研究项目都侧重于 开发针对所有医学相关变种的广谱快速作用疫苗或疗法 丝状病毒的种类。RP1使用基于重组水疱性口炎病毒(VSV)的快速作用疫苗， RP2专注于全人抗丝病毒单抗，RP3专注于抗丝病毒小分子抗体 干扰RNA、小分子抗病毒药物和联合治疗。这个中心的一个独特之处是 这些方法代表了一小部分医学对策，它们已经显示出有能力 为非人灵长类动物(NHP)提供完整的单次注射疫苗或治疗性保护，以防止 丝状病毒。所有三个中心研究项目都要求在动物身上评估针对 传染性丝状病毒。联邦法律要求丝状病毒在批准的生物安全级别(BSL)-4中处理 安全壳实验室。核心B提供经批准的BSL-4设施和一支训练有素且经验丰富的团队 BSL-4调查人员和工作人员进行支持RP1-RP3的研究。核心B将执行“有据可查的” NHP功效研究以及将根据以GLP为基础进行的“关键”NHP研究 质量协议，并将由专门的质量保证/质量控制小组提供支持。这些服务 由Core B提供的服务将包括1)安全的BSL-4丝状病毒种子库；2) 体外抗病毒活性分析；3)采购UTMB IACUC动物方案；3)采购， 动物的饲养和饲养；5)病毒的挑战、治疗和动物样本的收集；6) 对样本进行临床病理和病毒学分析的技术专长和设备 在BLS-4容器中进行尸检；7)从受感染动物身上收集组织进行组织病理学分析 8)对从国家卫生计划研究中收集的所有记录和数据进行质量系统管理。

PROJECT SUMMARY/ABSTRACT – BSL-4 Evaluation Core (Core B) Among viruses that cause disease in humans the filoviruses, Ebolavirus and Marburgvirus, stand out for their impressive lethality. These viruses are the most deadly human pathogens known to man with reported case fatality rates of up to 90%. The recent unprecedented 2013-16 epidemic of Zaire ebolavirus in West Africa resulting in over 28,000 cases and 11,000 deaths demonstrates the ability of filoviruses to emerge in new regions. In addition to natural outbreaks, Ebolavirus and Marburgvirus are known to have been the subjects of former biological weapons programs and have the potential for deliberate misuse. Currently, there are no filovirus vaccines or treatments approved for human use. For these reasons Ebolavirus and Marburgvirus have recently been included as only two of eleven human pathogens on the new US Department of Health and Human Services (HHS) Tier 1 list of Category A select agents. All three of the Research Projects within the Center focus on developing broad spectrum rapid acting vaccines or therapeutics against all medically relevant variants and species of filoviruses. RP1 employs recombinant vesicular stomatitis virus (VSV)-based rapid acting vaccines, RP2 focuses on fully human anti-filovirus monoclonal antibodies, and RP3 focuses on anti-filovirus small interfering RNAs, small molecule antivirals, and combination treatments. A unique aspect of this Center is that these approaches represent a very small cohort of medical countermeasures that have shown the ability to provide complete single injection vaccination or therapeutic protection of nonhuman primates (NHPs) against filoviruses. All three Center Research Projects require that countermeasures be evaluated in animals against infectious filoviruses. Federal law requires that filoviruses be handled in an approved Biosafety Level (BSL)-4 containment laboratory. Core B 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. Core B will perform “well-documented” NHP efficacy studies and also “pivotal” NHP studies that will be conducted in accordance with a GLP-based quality agreement and will be supported by a dedicated quality assurance/quality control team. The services provided by Core B will include 1) a secure repository of well characterized seed stocks of BSL-4 filoviruses; 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 BLS-4 containment; 7) histopathological analysis of tissues collected from animals infected with filoviruses; and 8) quality systems management of all records and data collected from NHP studies.