Advancement of Vaccines and Treatments for Ebola and Marburg Virus Infections

总体-项目概要/摘要 在引起人类疾病的病毒中，丝状病毒、埃博拉病毒和马尔堡病毒因其独特的生物学特性而脱颖而出。 杀伤力惊人这些病毒是人类已知的最致命的人类病原体， 死亡率高达90%。2013- 2016年扎伊尔埃博拉病毒在西非前所未有的流行 导致超过28，000例病例和11，000例死亡，表明丝状病毒能够在新的 地区除了自然爆发外，已知埃博拉病毒和马尔堡病毒也是 前生物武器计划，并有可能被故意滥用。目前，没有丝状病毒 批准用于人类的疫苗或治疗。出于这些原因，埃博拉病毒和马尔堡病毒最近 在新的美国卫生与公众服务部的11种人类病原体中， (HHS)A类精选代理的第1层列表。所有三个研究项目（RP），包括中心的重点 开发针对所有医学相关变体的广谱速效疫苗或治疗剂， 丝状病毒科的种。RP 1采用基于重组水泡性口炎病毒（VSV）的速效 RP 2专注于全人源抗丝状病毒单克隆抗体，RP 3专注于抗丝状病毒 小干扰RNA、小分子抗病毒药物（GS-5734和法匹拉韦）和联合治疗。一 该中心的独特之处在于，这些方法代表了一个非常小的医疗对策队列 其已经显示出提供完整的单次注射疫苗接种或非人的治疗保护的能力， 灵长类动物对抗丝状病毒这种准备程度是我们的主要力量和相应优势。 中心丝状病毒感染疫苗和治疗进展中心的主要目标是 进行“有据可查”和“关键”的NHP研究，以促进所用产品的开发 用于广谱治疗丝状病毒感染。三个联络点之间的协同作用和合作， 管理核心和生物安全级别（BSL）-4核心通过设计内置于中心，因为所有三个RP 共同评估和联合收割机对策，以提高效率。质量体系数据管理 将用于制备晚期供试品和进行动物研究。

OVERALL - Project Summary/Abstract 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 Research Projects (RP) that comprise the Center focus on developing broad spectrum rapid acting vaccines or therapeutics against all medically relevant variants and species of the family Filoviridae. 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 (GS-5734 and favipiravir), 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 against filoviruses. This level of readiness is a major strength and consequential advantage of our Center. The primary objective of the Advancement of Vaccines and Treatments for Filovirus Infections Center is to perform “well documented” and also “pivotal” NHP studies that will facilitate the development of products used for the broad spectrum treatment of filovirus infections. The synergy and cooperation among the three RPs, the Administrative Core, and the Biosafety Level (BSL)-4 Core is built into the Center by design as all three RPs work together to assess and combine countermeasures for enhanced efficacy. Quality system data management will be employed in both the preparation of advanced stage test articles and in the conduct of animal studies.