Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesis

Yerkes 国家灵长类动物研究中心 I 型 IFN 在调节 COVID-19 诱导的炎症和发病机制中的作用

基本信息

批准号：
10400338
负责人：
JONATHAN S LEWIN
金额：
$ 124.28万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10400338
关键词：
Animal Housing Basic Science Behavioral Behavioral Research Biocompatible Materials Biology Biomedical Research Breeding Communities Consultations Development Discipline Ensure Faculty Funding Genetic Goals Grant Guidelines Health Housing Human Immunology Infrastructure International Knowledge Laboratory Research Mental disorders Microbiology Mission Neuropharmacology Neurosciences Pathology Personal Satisfaction Postdoctoral Fellow Primates Process Publications Reporting Research Research Infrastructure Research Personnel Research Training Resources Role Scientist Services Social Behavior Strategic Planning Translational Research United States National Institutes of Health Universities Visit animal facility animal resource base cognitive neuroscience data resource graduate student improved innovation laboratory facility medical specialties member multidisciplinary nervous system disorder nonhuman primate operation programs training opportunity undergraduate student

项目摘要

Revised Title: Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesis Revised Abstract: This is an administrative supplement from the Yerkes National Primate Research Center (YNPRC). The goal of the supplement is to conduct a study with a total of 30 rhesus macaques in which 15 CoV-infected “control” animals are compared to 15 CoV-infected macaques treated with type I IFN antagonist to increase disease severity. Recent studies suggest that a defective type-I IFN response may cause severe and life-threatening COVID-19 outcomes due to uncontrolled viral spread and excessive inflammation. SARS-CoV-2-infected rhesus macaques develop mild to moderate COVID, and the aim of the experimental treatment is to induce more severe disease in this NHP model to test potential therapeutics. An adaptive trial design is proposed to provide statistical power will using the fewest number of animals. A wide range of viral, molecular, cellular, immunological, and clinical endpoints will be collected from the animals at serial timepoints and several tissues/organs will also be sampled in serial necropsies in subsets of animals (terminal necropsies in all remaining animals). Many of these samples will be investigated histologically and/or via molecular and other approaches by two different labs to test and develop NPRC COVID-19 SOPs and assess reproducibility. Samples will also be bio-banked as resources for future use by other researchers. The investigative team and environment are considered excellent. The project is considered high priority due to its importance for understanding the inflammatory sequalae of COVID, developing a rhesus model of severe disease, and working across NPRCs and accessing relevant expertise to advance standardized SOPs. This work should provide an in depth understanding of pathogenesis and inflammatory pathways, which will be critical to testing candidate therapeutics and second/third generation vaccines.

修订标题： Yerkes国家灵长类动物研究中心I型IFN在调节Covid-19诱导注射和发病机理中的作用修订摘要：这是Yerkes国家灵长类动物研究中心（YNPRC）的行政补充。该补充剂的目的是进行一项研究，总共有30颗恒河猴，其中15种COV感染的“对照”动物与15种用I型IFN拮抗剂治疗的COV感染的猕猴进行了比较，以增加疾病的严重程度。最近的研究表明，由于不受控制的病毒扩散和过多的感染，IFN型反应有缺陷可能会导致严重且威胁生命的COVID-19结果。 SARS-COV-2感染的恒河猕猴会出现轻度至中度的互联物，实验治疗的目的是在这种NHP模型中诱导更严重的疾病来测试潜在的治疗。提出了一种自适应试验设计，以提供统计能力将使用最少的动物。在串行时间点的动物中将收集多种病毒，分子，细胞，免疫学和临床终点，并且在动物亚群（所有其余动物的末端颗粒球）的系列颗粒中也将在串行时间和几个组织/器官处收集。这些样品中的许多样本将通过两个不同的实验室通过分子和其他方法对组织学和/或其他方法进行研究，以测试和开发NPRC COVID-19-SOP和评估可重复性。样本还将作为其他研究人员将来使用的资源。调查团队和环境被认为是极好的。该项目被认为很高的优先级，因为其对了解Covid的炎症序列的重要性，开发了严重疾病的恒河猴模型，并在NPRC上工作并获得相关的专业知识以推进标准化的SOP。这项工作应深入了解发病机理和炎症途径，这对于测试候选治疗和第二代/第三代疫苗至关重要。