中文摘要：本研究将重组Fim H蛋白加入到粘膜性疫苗几丁糖（CS）-pVP1中，旨在激发机体对CVB3病毒引起的心肌炎产生抗有效的粘膜免疫反应和免疫保护作用。与单独使用CS- pVP1疫苗相比，FimH-CS-pVP1免疫后能显著提高CVB3特异性保护抗体IgA (sIgA)的浓度和中和抗体滴度，增强CVB3特异性IgA诱导产生B细胞的比例，增强肠系膜淋巴结（MLNs）T细胞免疫反应。FimH-CS-pVP1免疫组产生的抗CVB-3引起的心肌炎的保护作用更强，主要表现在有限的心肌损伤、病毒浓度低以及存活率高等。进一步研究表明，这种增强的免疫保护作用不仅归因于可增强粘膜抗原VP1表达的M靶向细胞的特性，而且也与粘膜佐剂FimH的作用有关。Fim H能够促进形成生发中心（GCs），激发产生IgA诱导因子活性和抗原呈递细胞（APCs）的成熟。研究构建了一个双功能粘膜免疫疫苗FimH-CS-pVP1，该疫苗能够有效诱导产生CVB-3特异性粘膜免疫保护反应，与CS-pVP1相比能够提供更好的预防CVB3引起的心肌炎的作用。
外文摘要：Viral myocarditis is a common clinical cardiovascular disease mainly induced by coxsackievirus B3 (CVB3) with no effective therapeutic measures. Induction of efficient mucosa] immune responses is very critical against CVB3-induced myocarditis. FimH is an Escherichia coli (E. coli)-derived protein, which possesses an M cell-targeting property and functions as a TLR4 agonist. In this study, we introduced the recombinant FimH protein, into our previously developed CVB3 mucosal vaccine chitosan (CS)-pVP1, aiming to provoke more efficient mucosal immune responses and immunoprotection against CVB3-induced myocarditis. Compared with the CS-pVP1 vaccine, immunization with FimH-CS-pVP1 remarkably increased the levels and neutralizing titers of CVB3-specific protective secretory IgA (sIgA), enhanced the frequency of CVB3-specific IgA-producing B cells and amplified mucosal T-cell immune responses in mesenteric lymph nodes (MLNs), although failing to significantly amplify CVB3-specific systemic immune responses. Consistently, FimH-CS-pVP1 group showed the enhanced immunoprotection against CVB3-induced myocarditis, evidenced by the indices of limited myocardial injury, reduced viral loads and enhanced survival rate. Further study showed that this enhanced immunoprotection was not only ascribed to its M cell-targeting property, which led to the enhanced mucosal antigen VP1 expression, but also associated with the mucosal adjuvant effect of FimH, which facilitated the formation of germinal centers (GCs), production of IgA-inducing factors and maturation of antigen-presenting cells (APCs). Taken together, here we developed a bi-functional mucosal vaccine FimH-CS-pVP1, which simultaneously possessed the M cell-targeting property and mucosal adjuvant ability, and we showed that FimH-CS-pVP1 could efficiently induce the higher levels of CVB3-specific protective mucosal immune responses and provide better prophylactic effects against CVB3-induced myocarditis than CS-pVP1.
外文关键词： Coxsackievirus B3; M cell-targeting; Mucosal adjuvant; Mucosal vaccine
作者：Fan, XM; Yue, Y; Xiong, SD
作者单位：苏州大学
期刊名称：ANTIVIRAL RESEARCH
期刊影响因子：4.909
出版年份：2017
出版刊次：4
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