T cell modulation of COVID-19 disease

COVID-19 疾病的 T 细胞调节

基本信息

批准号：
10491340
负责人：
Nicholas James Maness
金额：
$ 21.25万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-20 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10491340
关键词：
2019-nCoV Acute Respiratory Distress Syndrome Animals Antibodies Antiviral Agents Blood Blood Coagulation Disorders CD8-Positive T-Lymphocytes CD8B1 gene COVID-19 COVID-19 pandemic Cells Cessation of life Complement Complex Coronavirus Data Disease Disease Outcome Disease Progression Disease model Endothelial Cells Exhibits Future Generations Genetic Human Hyperactivity Immune Immune System Diseases Immune response In Vitro Individual Infection Infiltration Inflammatory Inflammatory Response Interleukin-6 Investigation Knowledge Lung Macaca Macaca mulatta Measures Mediator of activation protein Modeling Monoclonal Antibodies Myeloid Cells Natural Killer Cells Patients Pharmaceutical Preparations Play Pneumonia Proteins Protocols documentation Research Role SARS-CoV-2 infection Sampling Site Societies Symptoms T cell response T-Cell Depletion T-Lymphocyte Testing Therapeutic Time Vaccines Viral Virus anti-viral efficacy antigen-specific T cells cohort cytokine immunogenicity immunoregulation interest macrophage neutralizing antibody nonhuman primate novel coronavirus novel therapeutics novel vaccines preclinical trial prevent rational design remdesivir response therapy design vaccine platform

项目摘要

Project Summary/Abstract The novel coronavirus that emerged in late 2019, termed SARS-CoV-2, quickly spread throughout the world and has, to date, infected millions and killed hundreds of thousands. This virus is shockingly complex in that the majority of infected individuals show few overt symptoms (though some data suggest they may have lasting damage nonetheless) but are largely healthy. In contrast, a small fraction of infected individuals exhibit a range of serious symptoms including pneumonia, acute respiratory distress, clotting disorders, and even death. The mechanisms that underly mild versus severe symptoms are not fully understood but immune mechanisms appear to play a role. Thus, we need to understand the roles of particular immune cells in order to understand the disease and properly treat it. Of particular interest is the role of CD8 T cells (CTL) in disease outcome. In this project we will use the rhesus macaque model of SARS-CoV-2 infection to assess the importance of CTL and other CD8+ cells in disease. In aim 1, we will deplete animals of all cells that express the CD8a molecule, including CTL and NK cells, and assess their ability to clear the virus. In aim 2, we will target only CTL for depletion and likewise assess their importance. In aim 3, we will use cells in the lab to assess how CTL interact with virus infected cells. Together, this project will comprehensively assess the importance of CTL in COVID-19 disease or protection from it.

项目概要/摘要 2019 年底出现的新型冠状病毒（称为 SARS-CoV-2）迅速在全球传播迄今为止，已感染数百万人并导致数十万人死亡。这种病毒的复杂性令人震惊大多数感染者几乎没有表现出明显的症状（尽管一些数据表明他们可能有尽管如此，仍存在持久的损害）但基本上是健康的。相比之下，一小部分感染者表现出一系列严重症状，包括肺炎、急性呼吸窘迫、凝血障碍，甚至死亡。轻微症状与严重症状之间的机制尚不完全清楚，但免疫机制似乎发挥了作用。因此，我们需要了解特定免疫细胞的作用，以便了解疾病并正确治疗。特别令人感兴趣的是 CD8 T 细胞 (CTL) 在疾病中的作用结果。在本项目中，我们将使用 SARS-CoV-2 感染的恒河猴模型来评估 CTL 和其他 CD8+ 细胞在疾病中的重要性。在目标 1 中，我们将耗尽动物中所有表达 CD8a 分子，包括 CTL 和 NK 细胞，并评估它们清除病毒的能力。在目标 2 中，我们将仅针对 CTL 进行消耗，并同样评估其重要性。在目标 3 中，我们将使用实验室中的细胞评估 CTL 如何与病毒感染的细胞相互作用。该项目将共同全面评估 CTL 在 COVID-19 疾病或预防该疾病中的重要性。