重组戊型肝炎疫苗不同免疫程序诱导小鼠产生IgG抗体的变化趋势研究  

Dynamic changes in specific IgG antibodies induced by recombinant hepatitis E vaccine using different immunization strategies in mice

作　　者：张占东 佟雪莲 安超翔 边雅静 李媛媛 Zhang Zhandong;Tong Xuelian;An Chaoxiang;Bian Yajing;Li Yuanyuan(The Seventh Laboratory,National Vaccine and Serum Institute,Beijing 101111,China;Laboratory Animal Centre,National Vaccine and Serum Institute,Beijing 101111,China)

机构地区：[1]国药中生生物技术研究院有限公司第七研究室,北京101111 [2]国药中生生物技术研究院有限公司实验动物中心,北京101111

出　　处：《中华微生物学和免疫学杂志》2020年第11期863-869,共7页Chinese Journal of Microbiology and Immunology

摘　　要：目的观察不同免疫程序中BALB/c小鼠体内针对重组戊型肝炎疫苗的特异性IgG抗体含量的动态变化趋势。方法将戊型肝炎疫苗系列稀释后腹腔免疫BALB/c、C57BL/6、NIH和KM品系小鼠,筛选适宜的动物模型。将适宜的模型动物随机分为一针免疫组(0周免疫)、二针免疫组(0-4周免疫)、三针免疫组(0-4-12周免疫)和佐剂对照组(与各实验组免疫程序相同),眼内眦采血收集血清,对不同时间节点的血清抗体进行定量检测并分析其含量变化趋势。结果C57BL/6和KM这两个品系小鼠在免疫戊型肝炎疫苗后各剂量组抗体阳转率较高,显示应答过于敏感。BALB/c和NIH品系小鼠对各剂量组疫苗免疫应答程度比较适宜,抗体阳转率也呈现一定的剂量效应关系。本研究选用BALB/c小鼠作为动物模型。一针免疫组的BALB/c小鼠体内特异性IgG抗体含量在第10周左右达到峰值,为44.35 U/ml,下降后维持在(5.52~13.28)U/ml;二针免疫组在加强免疫后抗体迅速上升于第8周达到峰值,从第10周开始血清抗体浓度开始缓慢下降至平稳期,最终维持在(16.50~32.54)U/ml;三针免疫组在1~12周的血清抗体变化趋势与二针免疫组相似,第三针加强免疫使小鼠体内抗体含量明显增加,并且延长了抗体的衰减周期,其特异性IgG含量维持在(62.65~72.61)U/ml,分别是一针免疫组和二针免疫组的9倍和3倍。结论本研究确定了BALB/c小鼠适宜作为动物模型探究不同免疫程序中戊型肝炎疫苗特异性IgG抗体含量动态变化趋势,为进一步研究该疫苗的体内效力提供数据参考。Objective To observe the dynamic changes in specific IgG antibodies induced by recombinant hepatitis E vaccine using different immunization strategies in BALB/c mice.Methods BALB/c,C57BL/6,NIH and KM mice were immunized intraperitoneally with serially diluted hepatitis E vaccine to select a mouse strain appropriately responding to hepatitis E vaccine.Then the selected BALB/c mice were randomly divided into three experimental groups,one-dose immunization group(0 week),two-dose immunization group(0 and 4 weeks)and three-dose immunization group(0,4 and 12 weeks),and three adjuvant control groups with the same immunization strategy as the corresponding experimental group.Blood samples were collected from the intraocular canthus at different time points and serum antibody levels were detected quantitatively.Results The BALB/c and NIH mice had proper responses to hepatitis E vaccine administrated at different doses than the C57BL/6 and KM mice,and the antibody positive conversion rates also showed a certain dose-effect relationship.Thus,the BALB/c mice were used as the animal model.The level of specific IgG antibodies in BALB/c mice immunized with one dose of vaccine reached a peak of 44.35 U/ml around the 10th week after the immunization,and then maintained at(5.52-13.28)U/ml after a decrease.The antibody level in the two-dose immunization group increased rapidly after the second immunization and peaked at the 8th week.From the 10th week,it gradually decreased and maintained at(16.50-32.54)U/ml.The trend of antibody changes in the three-dose immunization group was similar to that of the two-dose immunization group during the first 12 weeks,but a significant increase was induced after the third immunization and the level maintained at(62.65-72.61)U/ml for a long time,which was about nine times higher than that of the one-dose immunization group and three times of the two-dose immunization group.Conclusions This study showed that BALB/c mice were suitable models to study the dynamic changes in specific IgG antibodies el

关 键 词：戊型肝炎疫苗 免疫程序 抗体 变化趋势 

分 类 号：R512.6[医药卫生—内科学]