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

• 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
• 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

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型干扰素在调节COVID-19诱导的炎症和发病机制中的作用 修订摘要： 这是耶基斯国家灵长类动物研究中心（YNPRC）的行政补充。该补充剂的目的是用总共30只恒河猴进行研究，其中将15只CoV感染的“对照”动物与15只用I型IFN拮抗剂治疗以增加疾病严重程度的CoV感染的猕猴进行比较。最近的研究表明，由于不受控制的病毒传播和过度炎症，有缺陷的I型IFN反应可能导致严重和危及生命的COVID-19结果。SARS-CoV-2感染的恒河猴发展为轻度至中度COVID，实验性治疗的目的是在这种NHP模型中诱导更严重的疾病，以测试潜在的治疗方法。提出了一种适应性试验设计，以使用最少数量的动物提供统计功效。将在连续时间点从动物中采集广泛的病毒、分子、细胞、免疫学和临床终点，还将在动物亚组的连续尸检中采集几种组织/器官样本（所有剩余动物的终末尸检）。其中许多样本将由两个不同的实验室进行组织学研究和/或通过分子和其他方法进行研究，以测试和制定NPRC COVID-19 SOP并评估重现性。样本也将作为其他研究人员未来使用的资源进行生物储存。调查团队和环境被认为是优秀的。该项目被认为是高度优先的，因为它对理解COVID的炎症后遗症、开发严重疾病的恒河猴模型、跨NPRC工作和获取相关专业知识以推进标准化SOP具有重要意义。这项工作应该提供对发病机制和炎症途径的深入了解，这对测试候选疗法和第二/第三代疫苗至关重要。