BALB/C小鼠对不同佐剂SARS灭活疫苗的早期免疫反应  

Early immunoresponse of BALB/C mice to inactivated SARS vaccines prepared with different adjuvants

作　　者：熊盛[1] 王一飞[2] 刘新建[1] 张美英[1] 张传海[1] 刘石生[1] 冉延超[1] 杨红宇[1] 李久香[1] 陆家海[2] 张庶民[3] 万卓越[4] 鄢心革[4] 郑焕英[4] 孟民杰[5] 范江林[6] 

机构地区：[1]暨南大学生物医药研究开发基地,广州510630 [2]中山大学公共卫生学院,广州510089 [3]中国药品生物制品检定所,北京100050 [4]广东省疾病预防控制中心,广州510300 [5]第一军医大学分子免疫研究所,广州510515 [6]日本筑波大学基础医学研究所

出　　处：《中国免疫学杂志》2004年第6期413-417,共5页Chinese Journal of Immunology

基　　金：广东省非典科技攻关专项 ( 2 0 0 3 2 3 E 461) ;教育部科技研究重点项目 ( 10 4181);广东省自然科学基金团队项目 (粤科基办 [2 0 0 3 ] 11号 ) ;广州市科技攻关项目 ( 2 0 0 3Z3 3 0 40 1)经费资助

摘　　要：目的 :研究含不同佐剂的SARS灭活疫苗免疫小鼠后 ,小鼠的早期细胞免疫和体液免疫反应。方法 :灭活的SARS冠状病毒F6 9株分别与弗氏佐剂、氢氧化铝、CpG佐剂配伍 ,制备灭活疫苗。接种 6周龄SPF级BALB C小鼠。定时采血 ,分析小鼠外周血中CD4 + 、CD8+ T细胞亚群动态变化 ,同时测定鼠血清中特异性IgG抗体及抗体的病毒中和活性。结果 :由3种佐剂制备的SARS灭活疫苗免疫小鼠后 ,CD4 + 、CD8+ T细胞百分比升高或无明显改变 ,CD4 CD8比值无显著性改变。其中 ,弗氏佐剂疫苗免疫小鼠的CD4 + T细胞百分比升高较明显 ,且在一段时间内 ,维持在一个较高的水平 ;铝佐剂疫苗免疫小鼠后 ,未观察到明显T细胞亚群改变 ;而CpG佐剂疫苗免疫小鼠的CD8+ T细胞百分比改变较其它佐剂疫苗改变更明显。与此相异的是 ,3种疫苗均可诱导小鼠产生较高滴度特异性IgG抗体 ,并且所产生的抗体具有中和活性。在初免后第 34天 ,3种佐剂组的IgG抗体滴度分别为 1∶1 2 80 0、1∶32 0 0和 1∶1 6 0 0 ,中和效价分别为 1∶2 5 6 0、1∶96 0和 1∶32 0。结论 :SARS灭活疫苗接种小鼠后 ,可诱导较强的体液免疫反应 ,同时轻度上调CD4 + 、CD8+ T细胞活性 ,程度因佐剂而异。Objective:To study the cellular and humoral immunoresponse of BALB/C mice to inactivated SARS vaccines prepared with 3 different adjuvants in early stage.Methods:Inactivated SARS Coronavirus (SARS-CoV)strain F69 was mixed with either Freund's adjuvant(FA),Al(OH) 3 or CpG adjuvant,so prepared inactivated SARS vaccines were inoculated to 3 groups of 6-weeks-old SPF BALB/C mice.Mice sera were collected from day 0 to day 34 post immunization.Changes of CD4 +,CD8 +T cells and CD4/CD8 value in peripheral blood of mice were observed,as well as the titers of SARS-CoV specific IgG and their neutralization activity were determined.Results:Percentages of CD4 +,CD8 +T cell of mice immunized with inactivated SARS vaccines increased at certain dates.The CD4/CD8 values had not significant change.In brief,CD4 +T cell increased more obviously and maintained longer period in mice immunized with FA vaccine than that in mice immunized with other vaccines.CD8 +T cell changed more obviously in mice immunized with CpG adjuvant vaccine.In addition,there were no significant changes of T cell subset in mice immunized with Al(OH) 3 adjuvant vaccine.As a contrast,mice immunized with either kind of vaccine exhibited high level of specific IgG antibody,which possessed of neutralization activity.On day 34,the titers of IgG in FA,Al(OH) 3 and CpG group were 1∶12 800,1∶3 200 and 1∶1 600,respectively.The neutralization titers of the 3 groups on day 34 were 1∶2 560,1∶960 and 1∶320 respectively.Conclusion:The inactivated SARS vaccines might stimulate stronger humoral immunoresponse,and slightly up-regulate the activities of CD4 + and CD8 +T cell in BALB/C mice.The intensity of immunoresponse depends on adjuvants used to prepare the vaccine.

关 键 词：SAPS 灭活疫苗 T细胞亚群 IGG抗体 中和活性 

分 类 号：R373.19[医药卫生—病原生物学]