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应用含CpG基序的寡核苷酸增强乙型肝炎病毒基因疫苗诱导的细胞免疫应答

李文波 姚志强 周永兴 冯志华

  【摘要】 目的 探讨人工合成的含CpG基序的寡核苷酸(ODN)作为佐剂对乙型肝炎病毒(HBV)基因疫苗诱导小鼠产生细胞免疫应答的影响。方法 构建编码HBV表面抗原蛋白S的重组真核表达质粒pCR3.1-S作为HBV基因疫苗,人工合成含CpG基序(motif)的硫代磷酸寡核苷酸作为佐剂,以Balb/c小鼠作为实验动物进行免疫接种;采用3H-TdR法、51Cr 4 h释放法等分别检测免疫小鼠的淋巴细胞增殖和杀伤功能。结果 与空载体对照组相比较,HBV基因疫苗诱发Balb/c小鼠产生较好的HBV特异的淋巴细胞增殖及杀伤效应(P<0.05);应用CpG ODN组与未应用组相比较,免疫小鼠产生更强的HBV特异性细胞免疫应答(P<0.05)。结论 CpG ODN作为佐剂可增强HBV基因疫苗诱导Balb/c小鼠产生细胞免疫应答。
  【关键词】含CpG基序的寡核苷酸;肝炎病毒,乙型;基因疫苗;细胞免疫应答

CpG oligodeoxyribonucleotide potently enhances cellular immune responses induced by hepatitis B virus gene vaccines

LI Wenbo, YAO Zhiqiang, ZHOU Yongxing, et al.
(Department of Gastroenterology, General Hospital of Jinan Military Region, Jinan 250031, China)

  【Abstract】 Objective To investigate the effects of CpG oligodeoxyribonucleotide (ODN) as adjuvants on cellular immune responses in mice immunized with hepatitis B virus (HBV) gene vaccines. Methods Recombinant eukaryotic expression plasmids of pCR3.1-S encoding S protein of HBV were constructed as gene vaccines. Phosphorothioate oligodeoxynucleotides containing one CpG motif were synthesized as adjuvants. Then Balb/c mice were inoculated so that the immune responses to HBV could be studied. Lymphocyte proliferation reactions and cytotoxic T lymphocyte activities were detected through 3H-TdR incorporation and 4-hour 51Cr release assays. Results Compared with plasmid vectors of pCR3.1, HBV gene vaccines could induce strong lymphocyte proliferation reactions and cytotoxic T lymphocyte activities in immunized mice (P<0.05). Immunized mice with CpG ODN showed higher specific cellular responses to HBV than those without CpG ODN (P<0.05). Conclusion CpG ODN can act as adjuvants to enhence cellular immune responses in mice immunized with HBV gene vaccines.
  【Key words】CpG oligodeoxyribonucleotide; Hepatitis B virus; Gene vaccine; Cellular immunity response

  有研究表明,细胞免疫应答,包括辅助T细胞(Th)和细胞毒T细胞(CTL)应答,在机

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