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[乙肝核心抗原加前S1蛋白组成的治疗性疫苗对乙肝转基因小鼠慢性乙肝感染的免疫和病毒学疗效]

[Immunological and virological efficacy against HBV chronic infection of the therapeutic vaccine composed of HBV core plus PreS1 in HBV transgenic mice].

作者信息

Li Mei-zhong, Chen Xin-chun, Zhou Bo-ping, Le Xiao-hua, Xu Liu-mei, Wang Huo-sheng

机构信息

Shenzhen Institute of Hepatology, Shenzhen 518020, China.

出版信息

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2003 Sep;17(3):277-9.

Abstract

BACKGROUND

To investigate the immunological and virological efficacy of the therapeutic vaccine HBV CS1, a recombinant fusion protein which is composed of HBV core aa 1-155 plus PreS1 aa 3-55,against chronic HBV infection.

METHODS

HBV transgenic mice were immunized with HBV CS1(5 ug) emulsified in equal volume of complete Freund adjuvant on day 0, followed by a second vaccination with HBV CS1(5 ug) emulsified with incomplete Freund adjuvant on days 21. Mice of control group were mock-vaccinated with PBS plus complete Freund adjuvant/incomplete Freund adjuvant. The splenocytes of individual mouse were subjected to T cell proliferation assays by using 3Hg thymidine, HBsAg and HBV DNA in sera of mice were detected by ELISA and quantitative PCR, respectively.

RESULTS

HBV CS1 specific T cell response were induced in mice immunized with HBV CS1, with the titer of HBsAg and the level of HBV DNA decreased significantly after twice immunization with HBV CS1, while the control group almost remained the same.

CONCLUSION

HBV CS1 has the immunological and virological efficacy against chronic HBV infection in HBV transgenic mice; HBV CS1 could represent candidate vaccine for further studies on its role as therapeutic vaccine against HBV chronic infection in human.

摘要

背景

为研究治疗性疫苗HBV CS1(一种由乙肝病毒核心蛋白1-155氨基酸加上前S1蛋白3-55氨基酸组成的重组融合蛋白)对慢性乙肝病毒感染的免疫和病毒学疗效。

方法

在第0天,用等量完全弗氏佐剂乳化的HBV CS1(5微克)免疫乙肝病毒转基因小鼠,随后在第21天用不完全弗氏佐剂乳化的HBV CS1(5微克)进行第二次接种。对照组小鼠用PBS加完全弗氏佐剂/不完全弗氏佐剂进行模拟接种。通过使用3H-胸腺嘧啶对单个小鼠的脾细胞进行T细胞增殖试验,分别通过ELISA和定量PCR检测小鼠血清中的HBsAg和HBV DNA。

结果

用HBV CS1免疫的小鼠诱导出HBV CS1特异性T细胞反应,用HBV CS1两次免疫后,HBsAg滴度和HBV DNA水平显著下降,而对照组几乎保持不变。

结论

HBV CS1对乙肝病毒转基因小鼠的慢性乙肝病毒感染具有免疫和病毒学疗效;HBV CS1可作为候选疫苗,进一步研究其作为治疗人类慢性乙肝病毒感染疫苗的作用。

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