富含C、G碱基的核甘酸片段增强乙型肝炎表面抗原免疫反应  

CpG oligodeoxynucleotide enhances humoral and cellular immune responses against HBsAg in mice

作　　者：周智[1] 陈文思[2] 姚集鲁[2] 

机构地区：[1]重庆医科大学附属第二医院感染病科,400010 [2]中山大学附属第三医院传染病科

出　　处：《中华内科杂志》2003年第9期640-642,共3页Chinese Journal of Internal Medicine

基　　金：国家自然科学基金资助项目 (3 0 10 0 15 8);第 2 6届中国博士后基金资助项目 [(1999) 17]

摘　　要：目的　研究如何高效率激发机体对HBsAg的体液和细胞免疫反应 ,寻求治疗乙型肝炎的有效方法。方法　合成全硫代修饰的富含C、G碱基的核甘酸 (CpGODN)片段作为免疫佐剂 ,与HBsAg按一定比例混合免疫小鼠 ,研究其增强HBsAg免疫反应的作用。实验分为单纯HBsAg组、HBsAg +CpGODN组、商用乙肝疫苗 (与HBsAg亚型相同 )组、商用乙肝疫苗 +CpGODN组 4组。HBsAg及商用乙肝疫苗用量为 1 6 7μg/次 ,CpGODN为 16 5 μg/次。采用两剂免疫方案 ,间隔 15d ,末次免疫后 15d ,取血测抗 HBs ;取脾细胞作细胞毒性T淋巴细胞 (CTL)实验。结果　 4组抗 HBsA值分别为 0 10 9、0 4 35、0 4 2 2及 0 5 75 ;CTL反应值分别为 8 5 %、37 0 %、1 5 %和 2 8 0 % ,实验中未观察到明显的毒副作用。结论　 ( 1)CpGODN能明显增强HBsAg的体液免疫反应 ;( 2 )CpGODN也能增强HBsAg的细胞免疫反应 ;( 3)CpGODN与商用乙肝疫苗中的铝剂有协同作用 ,两者联用可同时诱导高效价的抗体反应和有效的细胞免疫反应。进一步评价其安全性和有效性 。Objective To induce stronger humoral and cell mediated immune response against HBsAg and seek more effective methods to treat hepatitis B virus infection.Methods 21 mer phosphorothioate oligodeoxynucleotide (ODN) and its control ODN were synthesized and used as an adjuvant of HBsAg and commercial hepatitis B vaccine to enhance their immune responses against HBsAg. Four groups of 33 mice received 2 doses of the mixtures (1.67 μg HBsAg : 16.5 μg CpG ODN) at an interval of 15 days. Group A: HBsAg only, 7 mice; group B: HBsAg+CpG ODN, 10 mice; group C: commercial hepatitis B vaccine, 6 mice; group D: commercial hepatitis B vaccine+CpG ODN, 10 mice. Serum anti HBs levels and cytotoxic T lymphocyte response (CTL) of splenocytes were assayed 15 days after the last vaccination.Results The mean absorbent values of blood anti HBs in the 4 groups were 0.109, 0 435, 0 422 and 0 575, respectively. The rates of CTL response were 8.5%, 37 0%, 1.5%, and 28 0%, respectively.Conclusions (1)CpG ODN markedly improves humoral (anti HBs) and cellular immune response (CTL) induced by HBsAg immunization. (2)There is a synergistic interaction between aluminum and CpG ODN in enhancing the humoral and cellular immune responses against HBsAg. Therefore, CpG ODN might be used to treat chronic hepatitis B virus infection after its safety and effectiveness have been confirmed.

关 键 词：核甘酸 碱基 乙型肝炎表面抗原 免疫反应 乙型肝炎病毒感染 

分 类 号：R392[医药卫生—免疫学]