C家族趋化因子XCL1增强CVB3基因疫苗的抗病毒免疫应答及保护作用

为提高以往构建的基因疫苗pcDNA3.1-VP1的抗B3型柯萨奇病毒(CVB3)感染的免疫效果,以编码C家族趋化因子XCL1的质粒pcDNA3.1-XCL1共注射,观察诱导的CVB3特异性免疫应答及CVB3病毒性心肌炎预防效果。将两种质粒各50μg混合后分别于0、2、4、6周肌注免疫小鼠4次,末次免疫后4周分别以5×LD50剂量CVB3攻击小鼠观察保护率,或以3×LD50剂量CVB3感染小鼠观察病毒性心肌炎的诱生。结果显示,与单纯pcDNA3.1-VP1质粒相比,XCL1质粒共注射可增强血清CVB3特异性IgG以及特异性CTL应答。5×LD50病毒攻击后,共注射组体重降低7.28%,而pcDNA3.1-VP1组体重降低10.97%;共注射组28 d保护率达40%,高于pcDNA3.1-VP1组的30%。3×LD50病毒感染后心肌组织病理显示,共注射组心外膜下仅有轻微炎症,心肌内未见炎症细胞浸润,而pcDNA3.1-VP1组除心外膜下有较多淋巴细胞聚集外,心肌内有少量炎症浸润和坏死灶。提示XCL1质粒共注射可增强CVB3特异性体液和细胞免疫应答及抗病毒保护,可有效预防病毒性心肌炎的发生。

Co-injection with XCL1 plasmid enhanced the protective immune response against CVB3 conferred by DNA vaccines

To enhance the effect of our previous constructed pcDNA3.1-VP1 DNA vaccine against Coxsackievirus B3(CVB3),another plasmid encoding XCL1,a C family chemokine,was intramuscularly co-injected.BALB/c mice were co-injected with 50 μg of pcDNA3.1-VP1 and pcDNA3.1-XCL1 4 times at 2 weeks intervals.Four weeks after the last immunization mice were challenged with 5×LD50 of CVB3 to see the the effect of ani-CVB3 protection or mice were infected with 3×LD50 of CVB3 to see the prevention of CVB3-myocarditis.The results showed that increased level of serum IgG and specific CTL response was induced after co-injection with pcDNA3.1-VP1 and pcDNA3.1-XCL1 compared to that induced by pcDNA3.1-VP1 alone.Mice receiving co-injection lost 7.28% of their weights after CVB3 challenge and resulted in 40% of protection,while mice injected with pcDNA3.1-VP1 alone lost 10.97% of their body weights and the protection percentage was 30%.Histopathological analysis showed that fewer inflammatory cells under the epicardium were observed in the hearts of co-immunized mice compared to that of control groups.In conclusion,co-injection with XCL1 plasmid could enhance CVB3 specific systemic immune responses and more efficiently prevent the occurrence of CVB3-induced myocarditis.