Advancement of Vaccines and Treatments for Ebola and Marburg Virus Infections

总体-项目摘要/摘要 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。构成中心焦点的所有三个研究项目(RP) 开发广谱速效疫苗或疗法，以对抗所有医学上相关的变种和 丝状病毒科的种类。RP1使用重组水疱性口炎病毒(VSV)为基础的快速作用 疫苗，RP2专注于全人抗丝状病毒单抗，RP3专注于抗丝状病毒 小干扰RNA、小分子抗病毒药物(GS-5734和法韦拉韦)以及联合治疗。一个 该中心的独特之处在于，这些方法只代表了一小部分医学对策 已经显示出有能力为非人类提供完整的单次注射疫苗或治疗性保护 灵长类动物对抗丝状病毒。这种准备程度是我们的一大优势和相应的优势 中心。丝状病毒感染中心疫苗和治疗进展的主要目标是 进行“有良好记录的”和“关键的”NHP研究，以促进所用产品的开发 用于丝状病毒感染的广谱治疗。三个注册会计师之间的协同与合作， 管理核心和生物安全级别(BSL)-4核心在设计上作为所有三个RP构建到中心中 共同评估和综合应对措施，以提高疗效。质量体系数据管理 将用于制备高级阶段试验文章和进行动物研究。

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.