Mucosal Immunization with High-Mobility Group Box 1 in Chitosan Enhances DNA Vaccine-Induced Protection against Coxsackievirus B3-Induced Myocarditis
Mucosal Immunization with High-Mobility Group Box 1 in Chitosan Enhances DNA Vaccine-Induced Protection against Coxsackievirus B3-Induced Myocarditis
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DOI：
10.1128/cvi.00466-13
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发表时间：
2013-09
影响因子：
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通讯作者：
Maowei Wang;Y. Yue;C. Dong;Xiaoyun Li;Wei Xu;S. Xiong
中科院分区：
文献类型：
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作者：
Maowei Wang;Y. Yue;C. Dong;Xiaoyun Li;Wei Xu;S. Xiong
柯萨奇病毒B3（Coxsackievirus B3，CVB 3）属于小核糖核酸病毒科，是一种小的单链RNA病毒。它的感染是心肌炎最常见的原因，没有可用的疫苗。胃肠道粘膜是CVB 3的主要进入通道，因此，在粘膜组织中诱导局部免疫可能有助于控制初始病毒感染并减轻随后的心肌损伤。在这里，我们评估的能力，高迁移率族蛋白1（HMGB 1）封装在壳聚糖颗粒，以增强粘膜免疫反应引起的柯萨奇B3病毒特异性粘膜DNA疫苗chitosan-pVP 1。用chitosan-pHMGB 1和chitosan-pVP 1质粒共免疫小鼠4次，间隔2周，最后一次免疫后4周用CVB 3攻击。与chitosan-pVP 1单独免疫组相比，chitosan-pHMGB 1联合免疫组能显著（P < 0.05）提高CVB 3特异性粪便分泌型伊加水平，促进黏膜T细胞免疫应答。相应地，在共免疫小鼠中观察到心肌炎严重程度降低，如显著（P < 0.05）降低的病毒载量、降低的心肌损伤和增加的存活率所证明的。流式细胞术分析表明，HMGB 1促进树突状细胞（DC）募集到肠系膜淋巴结，促进DC成熟，这可能是其粘膜佐剂效应的部分原因。这种策略可能代表了一种有前途的方法，候选疫苗对CVB 3诱导的心肌炎。
ABSTRACT Coxsackievirus B3 (CVB3), a small single-stranded RNA virus, belongs to the Picornaviridae family. Its infection is the most common cause of myocarditis, with no vaccine available. Gastrointestinal mucosa is the major entry port for CVB3; therefore, the induction of local immunity in mucosal tissues may help control initial viral infections and alleviate subsequent myocardial injury. Here we evaluated the ability of high-mobility group box 1 (HMGB1) encapsulated in chitosan particles to enhance the mucosal immune responses induced by the CVB3-specific mucosal DNA vaccine chitosan-pVP1. Mice were intranasally coimmunized with 4 doses of chitosan-pHMGB1 and chitosan-pVP1 plasmids, at 2-week intervals, and were challenged with CVB3 4 weeks after the last immunization. Compared with chitosan-pVP1 immunization alone, coimmunization with chitosan-pHMGB1 significantly (P < 0.05) enhanced CVB3-specific fecal secretory IgA levels and promoted mucosal T cell immune responses. In accordance, reduced severity of myocarditis was observed in coimmunized mice, as evidenced by significantly (P < 0.05) reduced viral loads, decreased myocardial injury, and increased survival rates. Flow cytometric analysis indicated that HMGB1 enhanced dendritic cell (DC) recruitment to mesenteric lymph nodes and promoted DC maturation, which might partly account for its mucosal adjuvant effect. This strategy may represent a promising approach to candidate vaccines against CVB3-induced myocarditis.