Enhanced resistance to coxsackievirus B3-induced myocarditis by intranasal co-immunization of lymphotactin gene encapsulated in chitosan particle.
Enhanced resistance to coxsackievirus B3-induced myocarditis by intranasal co-immunization of lymphotactin gene encapsulated in chitosan particle.
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DOI：
10.1016/j.virol.2009.01.029
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发表时间：
2009-04
期刊：
影响因子：
3.7
通讯作者：
Y. Yue;Wei Xu;Linkun Hu;Zhenggang Jiang;S. Xiong
中科院分区：
文献类型：
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作者：
Y. Yue;Wei Xu;Linkun Hu;Zhenggang Jiang;S. Xiong
柯萨奇病毒B3（Coxsackievirus B3，CVB 3）是一种引起人和小鼠心肌炎的胃肠道病毒。CVB 3-心肌炎的理想疫苗需要全身和粘膜区室的体液和细胞免疫。我们在这里描述了一种增强chitosan-pVP 1疫苗的策略，通过与壳聚糖颗粒包裹的T细胞趋化因子趋化因子（LTN）基因共免疫来提供对CVB 3的更高保护。分别以VP 1和LTN质粒包被的壳聚糖DNA疫苗滴鼻免疫小鼠4次，间隔2周，末次免疫后4周用CVB 3攻毒。与单独使用壳聚糖-pVP 1相比，壳聚糖-pLTN联合免疫显着增加血清和肠粘膜中高亲和力中和抗体水平，并促进全身和粘膜Th 1和CD 8 +CTL免疫反应。相应地，心肌病毒载量降低、心肌炎深度消退和存活率增加证明了对CVB 3-心肌炎的抵抗力增强。这种策略代表了一个有前途的平台，对粘膜感染性病原体的Th 1极化和保护。
Coxsackievirus B3 (CVB3) is a gastrointestinal virus causing myocarditis in human and mice. An ideal vaccine for CVB3-myocarditis requires both humoral and cellular immunity at systemic and mucosal compartments. We described here an enhancing strategy for chitosan-pVP1 vaccine by co-immunizing with lymphotactin (LTN) gene, a T cell-attractive-chemokine, encapsulated in chitosan particle to provide more protection against CVB3. Mice were intranasally co-immunized with 4 doses of chitosan–DNA vaccines separately encapsulating VP1 and LTN plasmids by 2 week-intervals and challenged with CVB3 4 weeks after the last immunization. Compared with chitosan-pVP1 alone, co-immunization with chitosan-pLTN significantly increased high-avidity-neutralizing antibody levels in serum and in intestinal mucosa, and promoted systemic and mucosal Th1 and CD8+CTL immune responses. Accordingly, enhanced resistance to CVB3-myocarditis was evidenced by reduced myocardial viral load, profound subsidence of myocarditis and increased survival rate. This strategy represents a promising platform for Th1 polarization and protection against mucosal infectious pathogens.