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.

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