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

一般来说，预防病毒感染的基本策略是诱导中和抗体。然而，这种策略可能不适用于丙型肝炎，因为没有已知的导致感染终止的中和抗体。细胞毒性T淋巴细胞（CTL）也能根除病毒感染。诱导CTL的方法不如诱导抗体的方法成熟。利用裸DNA编码靶抗原作为免疫原是一种诱导CTL的新方法。本研究的目的是测试该技术是否适用于丙型肝炎病毒。用编码丙型肝炎核心区的cDNA肌肉免疫小鼠。脾细胞呈丙型肝炎核心蛋白特异性增殖。脾细胞也用表达丙型肝炎核心蛋白的细胞系培养。培养的脾细胞对丙型肝炎核心表现出特异性CTL反应。提示DNA免疫方法适用于丙型肝炎病毒抗原。为了进一步分析，在更高水平上表达丙型肝炎病毒抗原的转基因小鼠系统正在建设中。

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.