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小鼠及家兔对丙型肝炎病毒多表位DNA疫苗免疫应答的研究

Immunogenicity of a multiple epitope antigen gene of hepatitis C virus in mice and rabbits

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【作者】 黄建生陈丽珊雷呈祥解咏梅张潜沈先荣贾福星张丽芸陈立茵郭明秋任大明

【Author】 HUANC Jian-sheng, CHEN Li-shan, LEI Cheng xiang, XIE Yong-mei, ZHANG Qian, SHEN Xian-rong, JIA Fu-xing, ZHANG Li-yun, Chen Li-yin, GUO Ming-qiu, REN Da-ming (School of Life Science, Fudan University; Institute of Navy Medicine, Shanghai 200433; Instituti

【机构】 复旦大学生命科学院!上海市邯郸路220号海军医学研究所!上海200433第一军医大学抗衰老研究室第一

【摘要】 目的探讨HCV复合多表位DNA疫苗的可行性。方法把HCV多表位抗原基因PCX克隆到真核表达载体pREP9(RSV启动子)及pCDNA3(CMV启动子)中,构建真核表达载体pREP9/PCX及pcDNA3/PCX。将其肌肉注射免疫小鼠及家兔,检测特异性体液免疫和细胞免疫的水平,并观察免疫小鼠的安全性。结果质粒pREP9/PCX及pcDNA3/PCX于免疫后第 6wk和第 10 wk时,开始可检测到抗 GZ-PCX IgG,随后抗体滴度逐渐升高,但水平较低,持续时间较短。pcDNA3/PCX肌肉注射免疫家兔后,于第8wk开始出现特异性抗体,至 3个月后滴度升至 1: 3 200,随后也开始下降。免疫小鼠及家兔可诱发针对GZ-PCX融合蛋白的迟发型超敏反应,并刺激淋巴细胞转化。免疫后小鼠的体重正常,肝脾脏未见明显肿大,具有良好的安全性。结论HCV多表位基因可诱发特异性免疫应答且安全性好,为HCV疫苗的研究提供了一定的理论及实验依据。

【Abstract】 Aim To explore the possibility of the multiple epitope DNA vaccines of hepatitis C virus (HCV). Methods A synthetic multiple epitope antigen gene PCX of HCV was cloned into vector pREP9(RSV promoter) and pcDNA3 (CMV promoter) to construct eukaryotic expression vectors pREP9/PCX and pcDNA3/PCX, then they were used to immunize mice and rabbits, the titer of specific humoral and cellular responses were detected and their safety were observed. Results In mice, specific anti-GZ-PCX antibody(IgG) was lower than 1: 1 000 and did not persist well. In rabbits, the highest titer of anti-GZ-PCX IgG reached at 1: 3 200 and remained for about one month. Delayed type hypersensitivity reactions (DTH)and proliferation response of peripheral lymphocytes were induced by GZ-PCX antigen. Body weights of immunized mice were normal and no obvious toxic reaction was observed. Conclusion The multiple epitope antigen gene of HCV could induce specific immune responses without obvious toxicity and it might be able to serve as an effective HCV vaccine candidate.

【基金】 国家自然科学基金资助!No.39780002
  • 【文献出处】 细胞与分子免疫学杂志 ,Journal of Cellular and Molecular Immunology , 编辑部邮箱 ,2001年01期
  • 【分类号】R392-33
  • 【被引频次】14
  • 【下载频次】67
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