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

• 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
• 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

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.

摘要 在引起人类疾病的病毒中，亨德拉病毒（HeV）和尼帕病毒（NiV）， 以其惊人的杀伤力脱颖而出这些病毒是已知的最致命的人类病原体之一， NIV的平均病死率约为75%。值得注意的是，有证据表明， 人与人之间的NIV传播除了HeV在澳大利亚的自然爆发和NiV主要在 在印度和孟加拉国，人们担心HeV和NiV可能被用作生物恐怖主义的媒介。目前， 还没有被批准用于人类的亨尼帕病毒疫苗或治疗。由于这些原因，尼帕和 亨尼帕病毒病是世界卫生组织新的研发项目中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/优先级- diseases/en/）. CETR内的所有三个研究项目都专注于开发广谱 针对HeV和NiV的疫苗或疗法。RP 1采用了HeV可溶性G（sG）疫苗， 目前在澳大利亚获得马匹许可。RP 2侧重于抗亨尼帕病毒单克隆抗体，RP 3侧重于抗亨尼帕病毒单克隆抗体。 集中于减毒亨尼帕病毒疫苗。该CETR的一个独特方面是，这些方法包括 最有希望的疫苗（HeV sG）和最有希望的抗病毒药物（人单克隆抗体m102.4） 已经显示出能够为非人灵长类动物提供完全的预防性和实验后保护 （NHP）分别针对亨尼帕病毒。所有三个CETR研究项目和核心B要求， 在动物中评估对策。联邦法律要求HeV和NiV在批准的 生物安全等级（BSL）-4级防护实验室。核心C提供一个批准的BSL-4设施和一个训练有素的， 由BSL-4研究者和工作人员组成的经验丰富的团队开展研究，支持RP 1-RP 3和核心B。 核心C将进行“记录良好”的NHP疗效研究和将进行的“关键”NHP研究 根据基于GLP的质量协议，该协议将由专门的质量 保证/质量控制团队。Core C提供的服务将包括：1）一个安全的 表征的BSL-4亨尼帕病毒的种子储备2）体外抗病毒活性测定; 3）UTMB的获得 IACUC批准动物方案; 3）动物的采购、圈养和饲养; 5）病毒攻击， 治疗和动物样本收集; 6）进行临床试验的技术专长和设备 对样本进行病理学和病毒学分析，并在BSL-4隔离区进行尸检; 7） 从感染亨尼帕病毒的动物收集的组织的组织病理学分析;和8）质量系统 管理从NHP研究中收集的所有记录和数据。 相关性 BSL-4评估核心（核心C）为RP 1、RP 2、RP 3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负责人和工作人员，科学咨询委员会， 和NIAID/NIH，以推进针对HeV和NiV的对策的发展。