Primate Core

灵长类核心

• 批准号: 7632085
• 负责人: ROGER A. VAN ANDEL
• 金额: $ 139.16万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7632085
• 关键词: Aerosols; Animal Model; Autopsy; Bacillus anthracis; Blood; Bronchoscopy; Development; Disease; Disease Outbreaks; Francisella tularensis; Functional disorder; HIV; Human; Incidence; Infection; Lung; Microbiology; Mission; Modeling; Mus; Population; Primates; Protocols documentation; Research Institute; Safety; Testing; Tissue Harvesting; Virulence; Virulent; biodefense; human disease; nonhuman primate; novel therapeutics; programs; respiratory; therapeutic vaccine

The incidence of primary pulmonary infections for most of the major biothreats is extremely low. Therefore, we will not be able to rely on testing new therapeutics and vaccines during "natural" outbreaks as is commonly done for many more common infections. Further, as is the case with the human immunodeficiency virus, direct challenges with the biothreats in normal human populations is unlikely to be a viable alternative. Because of these issues we will need to rely on animal models much more than usual for understanding the basic pathophysiology of the disease as well as determining the efficacy of new therapeutics and vaccines. The development of well-characterized nonhuman primate models that recapitulate human disease is extremely important to NIH's mission of biodefense. The combination of UNM and LRRI brings together significant expertise that makes this core very unique in its capabilities. The PI of this program project, Dr. Lyons, at UNMHSC has handled the biothreats for over 2 years and developed all of the protocols and safety requirements for appropriate handling and management of the select agents including Bacillus anthracis and virulent Francisella tularensis. This proposal intends to use both mice and nonhuman primates to identify mechanisms of virulence and host protection. It will combine the strengths in UNMHSC Microbiology with the aerosol and primate expertise of Lovelace Respiratory Research Institute. Specifically the non-human primate core will: 1) Develop reproducible aerosol models in non-human primates for virulent Francisella tularensis and Bacillus anthracis. 2) Perform aerosol challenges, necropsy and tissue harvesting for the aims in Project 1 and 3.

大多数主要生物威胁的原发性肺部感染发生率极低。因此，我们将无法像对许多更常见的感染通常所做的那样，在“自然”爆发期间依赖测试新的疗法和疫苗。此外，与人类免疫缺陷病毒的情况一样，在正常人群中直接挑战生物威胁不太可能是可行的替代方案。由于这些问题，我们将需要比平常更多地依赖动物模型来了解该疾病的基本病理生理学以及确定新疗法和疫苗的功效。开发能够重现人类疾病的特征良好的非人类灵长类动物模型对于 NIH 的生物防御使命极其重要。 UNM 和 LRRI 的结合汇集了重要的专业知识，使该核心的能力非常独特。该计划项目的 PI，UNMHSC 的 Lyons 博士，处理生物威胁已有 2 年多的时间，并开发了所有 适当处理和管理包括炭疽杆菌和剧毒土拉弗朗西斯菌在内的选定病原体的方案和安全要求。该提案打算使用小鼠和非人类灵长类动物来确定毒力和宿主保护机制。它将把 UNMHSC 微生物学的优势与 Lovelace 呼吸研究所的气溶胶和灵长类动物专业知识结合起来。具体来说，非人类灵长类核心将： 1) 在非人类灵长类动物中开发可重复的气溶胶模型，用于检测有毒的土拉弗朗西斯菌和炭疽杆菌。 2) 为实现项目 1 和 3 的目标进行气溶胶挑战、尸检和组织采集。