Trained immunity in the prevention of viral myocarditis and pancreatitis

训练有素的免疫力预防病毒性心肌炎和胰腺炎

基本信息

批准号：
10515667
负责人：
Jay Reddy
金额：
$ 18.07万
依托单位：
UNIVERSITY OF NEBRASKA LINCOLN
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：
2021-11-01 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10515667
关键词：
2019-nCoV Address Adjuvant Affect Animals Antigens Antiviral Response Attention BCG Live Bacteria Biological Assay COVID-19 Cells Coxsackie B Viruses Coxsackie Viruses Data Derivation procedure Development Dilated Cardiomyopathy Disease Disease Outbreaks Encephalitis Enterovirus Enterovirus Infections Epigenetic Process Exanthema Exposure to Foot Diseases Foundations Freund&apos s Adjuvant Future Genus Mycobacterium Goals Health Heart Histocompatibility Antigens Class II Histologic Human Immune Immune response Immunity Immunization Immunize Immunologic Stimulation Individual Infant Infection Innate Immune Response Insulin-Dependent Diabetes Mellitus Lipopolysaccharides Macrophage Mediating Memory Meningitis Metabolic Methods Mission Molecular Molecular Structure Morbidity - disease rate Mouth Diseases Mycobacterium tuberculosis Myocarditis Natural Killer Cells Neutralization Tests Outcome Pancreas Pancreatitis Paralysed Parasites Pathogenicity Pathway interactions Patients Prevention Property Public Health Research Serotyping Stimulus T-Lymphocyte Testing Therapeutic Uses Training United States United States National Institutes of Health Vaccine Adjuvant Vaccinee Vaccines Viral Viral Proteins Viral Vaccines Virus Virus Diseases adaptive immune response beta-Glucans chromatin immunoprecipitation cytokine diabetic cardiomyopathy gene function improved incomplete Freund&apos s adjuvant innovation insulitis microbial monocyte mortality mycobacterial neutrophil novel prevent respiratory response small molecule success tool unvaccinated vaccine candidate vaccine response vaccine strategy vaccine trial viral myocarditis γδ T cells

项目摘要

PROJECT SUMMARY/ABSTRACT Enteroviruses, such as group B Coxsackieviruses, are common suspects in myocarditis and pancreatitis. However, no vaccines are currently available for these viruses, in part because multiple serotypes of Coxsackieviruses can induce similar diseases. Thus, exploration of alternative strategies to protect against them may have merit. The research team has made an unexpected observation that animals immunized with complete Freund’s adjuvant (CFA) were completely protected from both myocarditis and pancreatitis induced with Coxsackievirus B3 (CVB) pointed to a possibility that trained immunity may be an underlying mechanism of CFA-mediated effects, as demonstrated with the Bacillus Calmette-Guérin (BCG). The long-term goal of this research is to identify adjuvants that induce trained immunity to enhance anti-viral vaccine responses in the prevention of enteroviral infections. The objective of this application is to determine if macrophages primed with CFA mediate trained immunity. The central hypothesis is that the CFA contributes to the induction of anti-viral responses by trained immunity. This hypothesis will be tested by two specific aims: 1) characterize anti-viral responses in animals immunized with CFA and 2) determine the mechanisms of CFA- mediated protection in CVB infection. Methods and tools to be used include multiplex cytokine bead array, virus neutralization test, and major histocompatibility complex class II dextramers to assess antigen-specific immune responses and chromatin immunoprecipitation and metabolite assays to investigate the mechanisms of CFA-induced trained immunity. The project is innovative because it aims to determine whether trained immunity offers protection against CVB infections. The proposed studies are significant because they will: 1) mechanistically investigate whether trained immunity is sufficient to prevent enterovirus infections and 2) identify pathways that contribute to CFA-induced trained immunity. These outcomes may have a significant impact on strategies for preventing and/or treating viral infections using mycobacterial components that are known to possess immune-stimulating properties.

项目概要/摘要肠道病毒，例如 B 组柯萨奇病毒，是心肌炎和胰腺炎的常见致病菌。然而，目前还没有针对这些病毒的疫苗，部分原因是多种血清型柯萨奇病毒可以诱发类似的疾病，因此，需要探索替代策略来预防。研究小组得出了一个意想不到的观察结果：动物接种了疫苗。完全弗氏佐剂（CFA）完全保护免受心肌炎和胰腺炎诱发柯萨奇病毒 B3 (CVB) 指出训练有素的免疫力可能是潜在机制的可能性卡介苗 (BCG) 所证明的 CFA 介导的作用的长期目标。这项研究的目的是确定可诱导训练有素的免疫力以增强抗病毒疫苗反应的佐剂该应用的目的是确定巨噬细胞是否预防肠道病毒感染。 CFA 介导训练有素的免疫力核心假设是 CFA 有助于免疫。通过训练有素的免疫力诱导抗病毒反应。该假设将通过两个具体目标进行检验：1）表征 CFA 免疫动物的抗病毒反应，2) 确定 CFA 的机制使用的方法和工具包括多重细胞因子珠阵列、病毒中和试验和主要组织相容性复合物 II 类右旋聚体以评估抗原特异性免疫反应和染色质免疫沉淀和代谢物测定以研究其机制该项目具有创新性，因为它旨在确定是否经过训练。免疫可以预防 CVB 感染，拟议的研究意义重大，因为它们将： 1) 从机制上研究训练有素的免疫力是否足以预防肠道病毒感染；2) 确定有助于 CFA 诱导的训练免疫力的途径，这些结果可能具有重要意义。对使用分枝杆菌成分预防和/或治疗病毒感染的策略的影响已知具有免疫刺激特性。