新型CpG ODN增强乙肝疫苗诱导IgG2a类抗体产生的实验研究①.doc

新型CpG ODN增强乙肝疫苗诱导IgG2a类抗体产生的实验研究① 【摘要】 目的：寻找能增强乙肝疫苗刺激IgG2a类抗体产生，使机体处于Th1样免疫环境的新型乙肝疫苗佐剂。方法：选用自行设计的A、B、C型CpG ODN，并以发表的A、B型CpG ODN作为阳性对照，与重组乙肝疫苗混合后于第0、4周免疫BALB/c小鼠，用ELISA法检测免疫小鼠血清中HBsAb水平及种类。结果：各型CpG ODN都能增强乙肝疫苗刺激HBsAb的产生水平，CpG ODN+乙肝疫苗免疫的小鼠血清中HBsAb类型为IgG2aIgG1，而单独应用商品化重组乙型肝炎疫苗的小鼠血清中HBsAb类型为IgG1IgG2a。结论：各型CpG ODN对重组乙型肝炎疫苗 ［含Al(OH)3佐剂］均具有增效作用，而且可以诱导机体产生倾向于Th1途径的免疫应答反应。 【关键词】 CpG ODN；乙型肝炎疫苗；佐剂；IgG2a Study of New CpG ODNs on enhancement of IgG2a production induced by hepatitis B vaccine CONG ZhongYi, BAO MuSheng, WAN Min, WANG Li, LI DaPeng, WANG LiYing, YU YongLi. Department of Immunology and Department of Molecular Biology, The School of Basic Medical Sciences of Jilin University, Changchun 130021, China ［Abstract］ Objective:To search for new adjuvant for hepatitis B vaccine that could stimulate the production of IgG2a and induce Th1like immune circumstance.Methods:BALB/c mice were immunized with recombinant hepatitis B vaccine only or combined with CpG ODNs designed by our lab(including type A, B and C) and CpG ODNs published in articles at 0th and 4th week. The HBsAb level and the IgG subsets in the serum of mice were measured by ELISA.Results:All types of CpG ODN could enhance the production of HBsAb stimulated by hepatitis B vaccine. The level of IgG subsets of mice immunized with hepatitis B vaccine combined with CpG ODN was IgG2aIgG1, and that of mice immunized with hepatitis B vaccine only was IgG1IgG2a.Conclusion:All types of CpG ODN can enhance the effect of recombinant hepatitis B vaccine and induce Th1like immune response. ［Key words］ CpG ODN；Hepatitis B vaccine；Adjuvant；IgG2a 细菌DNA和合成的含有非甲基化免疫刺激性CpG基序的寡聚脱氧核糖核酸（CpG oligodeoxynucleotides, CpG ODN）能作用于淋巴细胞、单核细胞和树突状细胞，刺激其增生、成熟以及分泌多种细胞因子、趋化因子和/或免疫球蛋白（Immunoglobulin, Ig） ［1］。具有免疫刺激性的CpG ODN至少有3种不同的类型：A型CpG ODN能强烈激活天然杀伤细胞，以及诱导浆细胞样树突状细胞前体表达alpha;干扰素。在结构上，A型CpG ODN的内部具有通过磷酸二酯键连接的含有CpG的回文序列，并且其3prime;和5prime;末端有磷酸硫代修饰的poly G（硫代修饰：磷酸二酯键中与磷原子结合的一个氧原子被硫原子代替，此修饰使CpG ODN能够抵抗DNA酶的作用，在体内半衰期延长，因A型CpG ODN全部硫代修饰会影响