应用包裹在纳米粒中的CpG脱氧寡核苷酸增强对乙肝疫苗的免疫应答  

The enhanced immune responses induced by chitosan-CpG ODN nanoparticles with hepatitis B vaccine on mice

作　　者：向一[1] 余青松 徐顺清[1] 祁智[1] 周漠炯[1] 

机构地区：[1]华中科技大学同济医学院,湖北武汉430030 [2]协和医院耳科,湖北武汉430030

出　　处：《中国医院药学杂志》2007年第2期143-145,共3页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金资助项目(编号:30170051)

摘　　要：目的:探讨应用包裹在壳聚糖纳米粒中的胞嘧啶-鸟嘌呤的脱氧寡核苷酸(CpG ODN)增强小鼠对乙肝疫苗的免疫应答。方法:采用复凝聚方法制备CpG ODN壳聚糖纳米粒。乙肝疫苗单用或联合CpG ODN免疫小鼠,用ELISA法检测抗HBs水平,流式细胞仪检测外周血CD4+、CD8+T淋巴细胞亚群,MTT法检测脾淋巴细胞增殖活性。结果:CpG ODN联合乙肝疫苗组抗HBs水平较单用乙肝疫苗组明显升高,且以CpG ODN壳聚糖纳米粒联合组产生的抗HBs水平最高;T淋巴细胞亚群分析显示,CpG ODN纳米粒联合组的CD4+T淋巴细胞百分比和CD4+/CD8+比值明显高于单用乙肝疫苗组;CpG ODN纳米粒联合组的脾淋巴细胞刺激指数明显高于其他组。结论:CpG ODN壳聚糖纳米粒联合乙肝疫苗不仅能诱导出高水平的抗HBs,且对细胞免疫也有调节作用。OBJECTIVE To investigate the effects of CpG ODN prepared by chitosan nanoparticles on immune response in BALB/c mice with hepatitis B vaccine. METHODS Chitosan-CpG ODN nanoparticles were prepared by complex coacervation method. The same doses of hepatitis B vaccine with or without CpG ODiN were injected into immune mice The serum anti-HBs levels in mice were detected by ELISA assays in three weeks after the second injection. Changes of peripheral blood T lymphocyte subsets CD4^＋ ,CD8^＋ were detected by flow cytometry. Proliferation of the spleen cells were detected by MTT. RESULTS The serum anti-HBs levels in mice injected by CpG ODN combining with hepatitis B vaccine were higher than that of the mice only injected by hepatitis B vaccine. Compared with the immunization with HBsAg plus CpG ODN, the immunization with HB- sAg plus CpG ODN nanoparticles had a significant increase in anti-HBs levels. Percentages of CD4^＋ and CD4^＋/CD8^＋ ratio of mice immunized with hepatitis B vaccine plus CpG ODN nanoparticles increased more than that only with hepatitis B vaccine. In addition,the spleen cells obtained from mice immunized with CpG ODN nanoparticles showed higher specific proliferative response. CONCLUSION Chitosan-CpG ODN nanoparticles combining with hepatitis B vaccine not only induce the high level of anti-HBs, but also can enhance the cellular immune response in mice.

关 键 词：乙肝表面抗原 壳聚糖纳米粒 CpG脱氧寡核苷酸 

分 类 号：R977.6[医药卫生—药品]