轮状病毒灭活疫苗和减毒活疫苗序贯免疫的体液免疫应答效果

目的:评价采用轮状病毒灭活疫苗进行初始免疫,减毒活疫苗进行加强免疫的序贯免疫方案的体液免疫应答效果。方法:将实验小鼠随机分为4组(口服疫苗组、序贯疫苗组、口服对照组及序贯对照组),按相应方案免疫后,ELISA检测血清轮状病毒特异性IgG和IgA、肠道轮状病毒特异性IgA;微量中和实验检测血清病毒特异性中和抗体;同时采用ELISA分析口服活疫苗后病毒排出情况。结果:与对照组相比,序贯疫苗组小鼠产生的轮状病毒特异性血清IgG、IgA、中和抗体及肠道IgA水平显著升高。与口服疫苗组相比,序贯疫苗组的免疫方案诱发的轮状病毒特异性血清IgG、IgA、中和抗体水平显著升高,肠道IgA水平两组间没有显著差异。同时,与口服疫苗组相比,序贯疫苗组中轮状病毒灭活疫苗进行的初始免疫未影响第一次口服活疫苗后病毒的排出量和排出时间,但序贯疫苗组第二次口服活疫苗后病毒的排出量迅速减少,排毒时间快速缩短,与口服疫苗组第三次服苗后病毒的排出量和排出时间相似。结论: 轮状病毒灭活疫苗和减毒活疫苗序贯免疫可有效诱发小鼠全身和黏膜局部的体液免疫应答,该方案将有可能成为轮状病毒疫苗临床应用的候选方案。

Effects of Humoral Immune Response Vaccinated by Sequential Inactivated-live Rotavirus Vaccine

Objective: To evaluate the humoral immune responses vaccinated by sequential inactivated-live rotavirus vaccines, primary immune with inactivated rotavirus vaccine (IRV) and boost immune with live rotavirus vaccine. Methods: The mice were randomly divided into four groups (oral vaccine group, sequential vaccine group, oral control group and sequential control group) and immunized by respective protocols. Then, the levels of serum rotavirus specific IgG, IgA and fecal rotavirus specific IgA were assessed by ELISA, the levels of serum neutralizing antibody were measured by microneutralization assay, the rotavirus sheddings in fecal following live rotavirus vaccine vaccination were assessed by ELISA. Results: Compared to sequential control groups, the levels of serum IgG, IgA, neutralizing antibody and fecal IgA were higher in sequential vaccine groups. Compared to oral vaccine groups, sequential vaccination induced the higher levels of serum IgG, IgA, neutralizing antibody, but there was no significant difference for the levels of fecal IgA between two groups. At the same time, it was found that there were no significant differences for the amounts and time of rotavirus shedding after first vaccination of live rotavirus vaccine between sequential vaccine groups and oral vaccine groups. However, after second vaccination of live rotavirus vaccine in sequential vaccine groups, the amounts and time of rotavirus shedding rapidly decrease, which were similar to the rotavirus shedding after third vaccination of live rotavirus vaccine in live vaccine groups. Conclusion: The systemic and mucosal humoral immune responses were induced by sequential inactivated-live rotavirus vaccines in mice. The protocol of vaccination with sequential inactivated-live rotavirus vaccines may be used as a candidate protocol for clinic application of rotavirus vaccine in the future.