Core C - The University of Texas Medical Branch at Galveston

核心 C - 德克萨斯大学加尔维斯顿医学分校

基本信息

批准号：
10362729
负责人：
Thomas William Geisbert
金额：
$ 80.23万
依托单位：
HENRY M. JACKSON FDN FOR THE ADV MIL/MED
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：
2019-03-20 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10362729
关键词：
Advanced Development Advisory Committees Agreement Animal Husbandry Animals Attenuated Australia Autopsy Bangladesh Biological Assay Bioterrorism Blood specimen Case Fatality Rates Clinical Clinical Chemistry Clinical Pathology Containment Data Disease Disease Outbreaks Endotoxins Epidemic Equipment Equus caballus Evaluation Genomics Goals Hematology Hendra Virus Henipavirus Housing Human Human Resources IACUC In Vitro India Laboratories Laws Medical Monitor Monoclonal Antibodies Mycoplasma National Institute of Allergy and Infectious Disease Nipah Virus Pathologic Pathology Periodicity Persons Plaque Assay Preventive Protocols documentation Quality Control Recording of previous events Records Research Personnel Research Project Grants Resources Reverse Transcriptase Polymerase Chain Reaction Sampling Secure Seeds Services System Technical Expertise Testing Texas Therapeutic Tissue Sample Tissues Training United States National Institutes of Health Universities Vaccination Vaccines Viral Load result Virus Work World Health Organization animal tissue base biosafety level 4 facility design efficacy study experience human monoclonal antibodies human pathogen in vitro Assay man nonhuman primate pathogen quality assurance repository research and development sample collection sterility testing transmission process vaccine evaluation virology

项目摘要

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.

抽象的在引起人类疾病的病毒中，亨尼帕病毒、亨德拉病毒（HeV）和尼帕病毒（NiV），这些病毒以其令人印象深刻的杀伤力而闻名，是已知的最致命的人类病原体之一。男性的 NiV 病死率平均约为 75%。值得注意的是，有证据表明存在多轮感染。除了澳大利亚的 HeV 自然爆发和 NiV 的人际传播外，NiV 还主要发生在印度和孟加拉国目前担心 HeV 和 NiV 可能被用作生物恐怖主义的媒介。由于这些原因，没有批准用于人类使用的亨尼帕病毒疫苗或治疗方法。亨尼帕病毒性疾病是世界卫生组织新研发报告中列出的仅有的八种病原体之一需要紧急研发行动的流行病威胁蓝图清单（http://www.who.int/blueprint/priority- CETR 内的所有三个研究项目都侧重于开发广泛的谱系。针对 HeV 和 NiV 的疫苗或疗法采用基于 HeV 可溶性 G (sG) 的疫苗。目前在澳大利亚获得马匹使用许可的 RP2 专注于抗亨尼帕病毒单克隆抗体，而 RP3 则专注于抗亨尼帕病毒单克隆抗体。该 CETR 的一个独特之处是这些方法包括减毒亨尼帕病毒疫苗。最有前途的疫苗（HeV sG）和最有前途的抗病毒药物（人单克隆抗体 m102.4）已显示出能够为非人类灵长类动物提供全面的暴露后保护 (NHP) 分别针对亨尼帕病毒所有三个 CETR 研究项目和核心 B 都要求这样做。联邦法律要求在经批准的情况下处理 HeV 和 NiV。生物安全级别 (BSL)-4 遏制实验室 Core C 提供经批准的 BSL-4 设施和经过培训的合格实验室。由 BSL-4 研究人员和工作人员组成的经验丰富的团队进行支持 RP1-RP3 和核心 B 的研究。核心 C 将进行“有据可查的”NHP 功效研究和将要进行的“关键”NHP 研究符合基于 GLP 的质量协议，该协议将得到专门质量人员的支持 Core C 提供的服务包括 1) 安全的油井存储库。 BSL-4 亨尼帕病毒种子库的特征 2) 体外抗病毒活性测定 3) UTMB 的采购； IACUC 批准动物方案；3) 动物的采购、饲养和饲养；5) 病毒挑战，治疗和动物样本采集；6) 临床实施的技术专业知识和设备；对样本进行病理学和病毒学分析，并在 BSL-4 收容区内进行尸检；7) 对从感染亨尼帕病毒的动物身上采集的组织进行组织病理学分析；8) 质量体系；管理从 NHP 研究收集的所有记录和数据。关联 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领导者和工作人员、科学顾问委员会、与 NIAID/NIH 共同推进 HeV 和 NiV 对策的制定。