水疱性口炎病毒VSV为载体的新型病毒性心肌炎疫苗的制备及免疫机制的初步研究.pdfVIP

英文摘要 水疱性口炎病毒VSV 为载体的新型病毒性心肌炎疫苗的制备及免疫机制的初步研究 The generation of a vesicular stomatitis virus-based vaccine and characterization of its immune responses against CVB3 induced viral myocarditis Abstract Coxsackievirus B3 (CVB3) is an important etiological agent of acute, chronic viral myocarditis, and dilated cardiomyopathy (DCM). CVB3, along with other enteroviruses, is involved in about 50% of myocarditis cases and in the pathogenesis of dilated cardiomyopathy. Prevention of CVB3 infection is therefore highly desirable. Although vaccination against CVB3 could significantly reduce the incidence of serious or fatal viral myocarditis and various other diseases associated with CVB3 infection, there is currently no vaccine or therapeutic reagent in clinical use. In this study, we applied vesicular stomatitis virus (VSV) as a vector for the development of a novel CVB3 vaccine. A recombinant VSV expressing CVB3 major immunogen VP1 has been generated and the immune protection elicited by VSV-VP1 was evaluated. We demonstrated that intranasal delivery of VSV-VP1 is able to induce potent antigen specific mucosal immune response as well as systemic immune response, particularly the induction of polyfunctional T cells. Importantly, mice immunized with VSV-VP1 were protected more than those receiving VSV-GFP or chitosan formulated DNA mucosal vaccine. The increased dendritic cells (DCs) maturation measured in mesenteric lymph node (MLN) could be a potential mechanism that VSV-VP1 vaccination produces extraordinary protective