Advancement of Vaccines and Treatments for Ebola and Marburg Virus Infections

埃博拉和马尔堡病毒感染疫苗和治疗的进展

基本信息

批准号：
10356834
负责人：
Thomas William Geisbert
金额：
$ 704.32万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-08 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10356834
关键词：
Advanced Development Africa Angola Animals Antiviral Agents Bundibugyo virus Case Fatality Rates Case Study Categories Category A pathogen Cells Cessation of life Combined Modality Therapy Congo Consequentialism Data Management Resources Disease Disease Outbreaks Ebola virus Epidemic Family Filoviridae Infections Filovirus Goals Health Human Infrastructure Injections Intervention Journals Laboratories Licensure Marburgvirus Medical Microbiology Monoclonal Antibodies Nature Needlestick Injuries Pongidae Population Preparation Preventive vaccine Publications Readiness Recombinants Research Project Grants Risk Services Small Interfering RNA Sudan Ebola virus Testing Therapeutic Therapeutic Intervention Translational Research Treatment Efficacy United States Dept. of Health and Human Services Vaccination Vaccines Variant Vesicular stomatitis Indiana virus Virus Virus Diseases Work Zaire Ebola virus animal rule base biosafety level 4 facility bioweapon clinical investigation cohort combat design drug discovery high risk human monoclonal antibodies human pathogen improved lead candidate man mass casualty medical countermeasure nonhuman primate product development programs protective efficacy remdesivir small molecule synergism translational medicine vaccine candidate

项目摘要

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.

总体 - 项目摘要/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致病性而脱颖而出。这些病毒是已知病例中最致命的人类病原体。 2013-16 年西非爆发了史无前例的扎伊尔埃博拉病毒疫情，死亡率高达 90%。导致超过 28,000 例病例和 11,000 例死亡，这表明丝状病毒有能力在新的环境中出现除了自然爆发外，已知埃博拉病毒和马尔堡病毒也是该病毒的传播对象。以前的生物武器计划，有可能被故意滥用。目前，还没有丝状病毒。由于这些原因，埃博拉病毒和马尔堡病毒最近被批准用于人类。在新的美国卫生与公共服务部中，仅将其列为人类病原体中的 2-11 种 (HHS) A 类选定代理的一级列表构成中心重点的所有三个研究项目 (RP)。开发针对所有医学相关变异的广谱快速作用疫苗或疗法，以及 RP1 属于丝状病毒科，采用基于重组水泡性口炎病毒 (VSV) 的快速作用。疫苗方面，RP2专注于全人源抗丝状病毒单克隆抗体，RP3专注于抗丝状病毒小干扰 RNA、小分子抗病毒药物（GS-5734 和法匹拉韦）以及联合治疗 A。该中心的独特之处在于，这些方法代表了一小部分医疗对策已显示出提供完整的单次注射疫苗接种或非人类治疗保护的能力这种针对丝状病毒的准备水平是我们的主要优势和必然优势。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”且“关键”的 NHP 研究，这将促进所用产品的开发三个RP之间的协同与合作，用于丝状病毒感染的广谱治疗。管理核心和生物安全级别 (BSL)-4 核心按照设计内置于中心，作为所有三个 RP 共同评估和结合提高质量体系数据管理效率的对策。将用于高级测试物品的准备和动物研究的进行。