人工合成免疫刺激DNA联合HBsAg DNA疫苗在HBV转基因鼠的免疫应答研究  

DNA mediated immunization co-injected with CpG-oligodeoxynucleotides in hepatitis B virus transgenic mice

作　　者：邓涛 范公忍 胡学玲 陈佩兰 陈乃玲 胡大荣 贾克明 

机构地区：[1]北京解放军肝病研究所,北京100700

出　　处：《中国免疫学杂志》2003年第3期149-153,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金资助 ( 3 9770 660 )

摘　　要：目的 :探讨免疫刺激DNA序列联合基因免疫在HBV转基因鼠的免疫应答。方法 :用人工合成硫代修饰的免疫刺激DNA寡核苷酸 (CpGODN)与HBVS区基因真核表达载体 (V HBs)联合免疫HBsAg转基因鼠 ,通过ELISA观察小鼠血清HBsAg及抗 HBs抗体水平 ,并用免疫组化 (SP法 )及病理HE染色观察小鼠肝组织HBsAg表达量的改变及肝组织炎症活动度。结果 :V HBs联合CpGODN组 6只免疫鼠中有 2只血清抗 HBs抗体阳性 ,其平均效价为 (5 6 2 1± 15 16 )mU ml,血清HBsAg浓度在免疫后第 8周时有 2只转阴 ,而单用V HBs组及V 10 12对照组小鼠血清抗 HBs抗体均阴性、HBsAg含量无明显降低。V HBs +CpGODN组肝组织HBsAg的表达量低于V HBs组及对照组 ,并可见大量炎细胞浸润 ,炎症组织活动度积分明显高于V HBs组及对照组。结论 :CpGODN联合V HBs可增强其免疫应答及抗病毒效应。Objective:To study the immune responses of HBV based immunization co injecting CpG oligodeoxynucleotides in HBV transgenic mice.Methods:The HBV transgenic mice were immunized by multiple sites intramuscular injection with V HBs and CpG ODN or V HBs alone or V 1012 controls.The anti HBs Ab and HBsAg in serum from immunized mice was measured by ELISA.The expression of HBsAg in liver tissue was detected by immunohistochemistry method(SP).The histological activity index was calculated with Knodell's method.Results:The anti HBs Ab in serum could be detected and HBsAg in serum and liver tissues could not be measured in 2 out of 6 HBV transgenic mice immunized with V HBs+CpG ODN.There were not significantly changes in the level of anti HBs Ab and HBsAg in serum from HBV transgenic mice immunized with V HBs or V 1012 alone.The histological activity indexes in liver tissues from mice immunized with V HBs+CpG ODN were higher than that in mice inoculated with V HBs or V 1012 alone.The large number of lymphocytes could be found in liver tissues in V HBs+CpG ODN immunization group by microscopy.Conclusion:The immuno response,which seems to be responsible for the disappearance of HBsAg,might be elicited in HBV transgenic mice immunize with V HBs+CpG ODN.

关 键 词：乙肝病毒 基因免疫 免疫刺激DNA序列 转基因鼠 

分 类 号：R392.11[医药卫生—免疫学]