Trained immunity in the prevention of viral myocarditis and pancreatitis

项目摘要/摘要 肠道病毒，如B组柯萨奇病毒，是心肌炎和胰腺炎的常见嫌疑人。 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的 柯萨奇病毒也能引发类似的疾病。因此，探索替代战略以防止 他们或许有可取之处。研究小组出人意料地观察到，给动物接种疫苗的动物 完全弗氏佐剂(CFA)可完全预防心肌炎和胰腺炎 柯萨奇B3病毒(CVB)指出，训练有素的免疫可能是一种潜在的机制 卡介苗(BCG)证明了CFA介导的效应。的长期目标是 本研究旨在找出诱导训练性免疫以增强抗病毒疫苗应答的佐剂。 预防肠道病毒感染。这项应用的目的是确定巨噬细胞 拥有终审法院调解训练的豁免权。中心假设是终审法院对 通过训练免疫诱导抗病毒反应。这一假设将通过两个具体目标进行检验：1) 鉴定CFA免疫动物的抗病毒反应；2)确定CFA的作用机制。 CVB感染的介导性保护作用。要使用的方法和工具包括多路细胞因子珠阵列， 病毒中和试验和主要组织相容性复合体II类右旋糖体以评估抗原特异性 免疫反应、染色质免疫沉淀和代谢物分析探讨其作用机制 CFA诱导的训练有素的免疫。该项目具有创新性，因为它的目的是确定是否经过培训 免疫力提供了对CVB感染的保护。拟议的研究具有重要意义，因为它们将：1) 机械地调查训练有素的免疫力是否足以预防肠道病毒感染和2) 确定促进CFA诱导的训练性免疫的途径。这些结果可能会对 对使用分枝杆菌成分预防和/或治疗病毒感染的战略的影响 已知具有免疫刺激特性。

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.