Basic Study on DNA immunization against hepatitis C virus by using a transgenic mouse system

利用转基因小鼠系统进行丙型肝炎病毒DNA免疫的基础研究

• 批准号: 06670580
• 负责人: MORIYAMA Takashi
• 金额: $ 1.34万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670580/
• 关键词: HCV core protein; Cytotoxic T lymphocytes; DNA immunization

Basic strategy for prevention of viral infection is, in general, to induce neutralizing antibody. This strategey, however, may not apply to hepatitis C,because there is no known neutralizing antibody that leads to the termination of infection. Cytotoxic T lymphocytes (CTL) also eradicates viral infection. Methods of inducing CTL is not as well established as those of inducing antibodies. A new method of inducing CTL is to use a naked DNA coding target antigens as an immunogen. The objective of this study is to test whether this technology is applicable to hepatitis C virus.Mice were immunized with cDNA coding hepatitis C core region intramuscularly. Primed splenocytes showed a hepatitis C core protein specific proliferation. The splenocytes were also cultured with a cell line that expressed hepatitis C core protein. Cultured splenocytes showed specific CTL responses to hepatitis C core.These results suggest that the DNA immunization method is applicable to hepatitis C virus antigens. For further analysis, transgenic mouse systems that express hepatitis C virus antigens at a higher level are under construction.

预防病毒感染的基本策略通常是诱导中和抗体。然而，这一策略可能不适用于丙型肝炎，因为目前还没有已知的中和抗体可以终止感染。细胞毒性T淋巴细胞(CTL)还可以根除病毒感染。诱导CTL的方法不如诱导抗体的方法成熟。一种新的诱导CTL的方法是用编码靶抗原的裸露DNA作为免疫原。本研究的目的是验证该技术是否适用于丙型肝炎病毒，用编码丙型肝炎病毒核心区的基因片段肌肉免疫小鼠。活化的脾细胞表现出丙型肝炎核心蛋白的特异性增殖。脾细胞还与表达丙型肝炎病毒核心蛋白的细胞系共同培养。培养的脾细胞表现出对丙型肝炎病毒核心抗原的特异性CTL反应，提示该DNA免疫方法适用于丙型肝炎病毒抗原。为了进一步分析，更高水平表达丙型肝炎病毒抗原的转基因小鼠系统正在建设中。

项目成果

Harase, Ichiro: "Immune response to hepatitis C virus core protein in mice" Immunology and Cell Biology. 73. 346-352 (1995)

Harase，Ichiro：“小鼠对丙型肝炎病毒核心蛋白的免疫反应”免疫学和细胞生物学。

Kita,Hiroto: "Springer-Verlag.In Viral Hepatitis and Liver Disease" Recognition of hepatitis C virus nucleocapsid protein-derived peptides by cytotoxic T lymphocytes., 4 (1994)

Kita，Hiroto：“Springer-Verlag.In 病毒性肝炎和肝病”细胞毒性 T 淋巴细胞对丙型肝炎病毒核衣壳蛋白衍生肽的识别。，4 (1994)

Harase, Ichiro: "Immune response to hepatitis C virus core protein in mice" Immunlogy and Cell Biology. 73. 346-352 (1995)

Harase，Ichiro：“小鼠对丙型肝炎病毒核心蛋白的免疫反应”免疫学和细胞生物学。

Kita, Hiroto: "HLA B44-restricted cytotoxic T lymphocyte responses to the peptides of HCV nucleoprotein residues 81-100 in patients with chronic hepatitis C" Journal of Gastroenterology. 30. 809-812 (1995)

Kita，Hiroto：“慢性丙型肝炎患者 HLA B44 限制的细胞毒性 T 淋巴细胞对 HCV 核蛋白残基 81-100 肽的反应”胃肠病学杂志。

Kita,Hiroto: "HLA B44-restricted cytotoxic T lymphocyte responses to the pcptides of HCV nucleoprotein residues 81-100 in patients with chronic hepatitis C." Journal of Gastroenterology. 30. 809-812 (1995)

Kita, Hiroto：“慢性丙型肝炎患者 HLA B44 限制细胞毒性 T 淋巴细胞对 HCV 核蛋白残基 81-100 肽的反应。”