HMGB1不同结构域对CVB3心肌炎疫苗免疫增强作用的比较研究

Comparative analysis of immune enhancement effects of various HMGB1 domains following co-administration with CVB3-specific DNA vaccine

目的本研究在已构建好的柯萨奇病毒B3型(CVB3)疫苗pVP1的基础上,分别引入编码HMGB1不同结构域的质粒DNA,通过检测共免疫诱导的免疫应答强度,比较其各结构域介导的免疫增强作用。方法首先构建了编码HMGB1的不同结构域的质粒pHMGB1-A、B、C-box,分别与pVP1疫苗混合后肌注免疫小鼠,于末次免疫后10 d检测其诱导的特异性抗体和细胞免疫应答。结果与pVP1单独免疫组相比,pHMGB1-B box共免疫组可显著提高特异性血清IgG水平,同时也显著增加了脾脏IFN-γ+T的细胞数量;C-box仅显示出促进T细胞免疫的效应且程度较B-box小,对抗体水平无明显增强作用;A-box对抗体水平和细胞免疫应答的促进作用都不明显。结论 HMGB1不同结构域对病毒性心肌炎DNA疫苗诱导的体液和细胞免疫应答具有不同程度的增强效应,其中B-box可综合增强CVB3特异性体液和细胞免疫应答,C-box仅有促进T细胞应答效应,而对抗体水平无促进作用,A-box对抗体水平增加和细胞免疫应答的促进作用不明显。该研究不仅有助于深入了解HMGB1不同结构域的免疫佐剂效果差异,更为科学合理应用HMGB1增强免疫应答提供了一定的基础数据。

In this study, plasmids encoding HMGB1 various domains were introduced into previouslyprepared CVB3-specific DNA vaccines, and their immune enhancement effects were carefully detected and compared. Plasmids encoding HMGB1 A-, B-, and C-box domains were constructed. Following confirming them in vitro transfection efficiency, various HMGB1 domain plasmids were intramuscularly co-administrated with pVP1 vaccine at 10-days intervals for 3 times. 10 days after the last immunization, CVB3-specific serum IgG and splenic IFN-y^＋T cell immune responses were detected. Compared with pVP1 alone, HMGB1-B box co-administration significantly increased specific serum IgG levels and splenic T cell immune response, while HMGB1 C-box coadministrated group showed no enhancing on humoral response, only little enhancing on cellular immunity. A-box only showed little enhancing ability on cellular immunity and humoral response. Here, we showed that different HMGB1 domain distinct immune enhancement effects on CVB3-specific immune responses elicited by pVP1 vaccine. Our study not only paves the way to understand the diverse adjuvant abilities of HMGB1 domains, but also provide some clues to the rational application of HMGB1 as a vaccine adjuvant.