Liao Guoyang, Wang Yue, Chang Jinhai, Bian Tao, Tan Wenjie, Sun Mingbo, Li Weidong, Yang Huijuan, Chen Junying, Zhang Xinwen, Bi Shengli, Omata Masao, Jiang Shude
Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Yunnan Province, People's Republic of China.
Hepatology. 2008 Jan;47(1):25-34. doi: 10.1002/hep.21992.
DNA immunization has been used to induce either humoral or cellular immune responses against many antigens, including hepatitis C virus (HCV). In addition, DNA immunizations can be enhanced or modulated at the nucleotide level. Genetic immunizations were examined in BALB/c mice through the use of plasmids and chimeric DNA constructs encoding HCV core proteins and hepatitis B virus (HBV) precore (preC) regions. Plasmids encoding the truncated HCV core induced potent humoral and cellular responses to HCV; pcDNA3.0A-C154 produced a stronger antibody response than pcDNA3.0A-C191 (P < 0.01) and pcDNA3.0A-C69 (P < 0.05). HBV preC enhanced the humoral and cellular immune responses of BALB/c mice to HCV; however, pcDNA3.0A-C69preC resulted in a weak cytotoxic T lymphocyte (CTL) response. In addition, the humoral and cellular immune responses to HCV of groups immunized with pcDNA3.0A-C154preC and pcDNA3.0A-C191preC plasmids were higher than those of groups immunized with pcDNA3.0A-C154 and pcDNA3.0A-C191. In vivo CTL responses verified that mice immunized with preC core fused DNAs showed significantly high specific lysis compared with mice immunized with HCV cores only (P < 0.01). In our study, pcDNA3.0A-C154preC led to the highest immune response among all DNA constructs.
DNA that encodes truncated HCV core proteins may lead to increased immune responses in vivo, and these responses may be enhanced by HBV preC.
DNA免疫已被用于诱导针对包括丙型肝炎病毒（HCV）在内的多种抗原的体液或细胞免疫反应。此外，DNA免疫可在核苷酸水平上得到增强或调节。通过使用编码HCV核心蛋白和乙型肝炎病毒（HBV）前核心（preC）区域的质粒和嵌合DNA构建体，在BALB/c小鼠中检测了基因免疫。编码截短型HCV核心的质粒诱导了对HCV的强效体液和细胞反应；pcDNA3.0A-C154产生的抗体反应比pcDNA3.0A-C191（P < 0.01）和pcDNA3.0A-C69（P < 0.05）更强。HBV preC增强了BALB/c小鼠对HCV的体液和细胞免疫反应；然而，pcDNA3.0A-C69preC导致了较弱的细胞毒性T淋巴细胞（CTL）反应。此外，用pcDNA3.0A-C154preC和pcDNA3.0A-C191preC质粒免疫的组对HCV的体液和细胞免疫反应高于用pcDNA3.NA-C154和pcDNA3.0A-C191免疫的组。体内CTL反应证实，与仅用HCV核心免疫的小鼠相比，用preC核心融合DNA免疫的小鼠表现出显著更高的特异性裂解（P < 0.01）。在我们的研究中，pcDNA3.0A-C154preC在所有DNA构建体中引发了最高的免疫反应。
编码截短型HCV核心蛋白的DNA可能导致体内免疫反应增强，并且这些反应可能被HBV preC增强。
