Lee S W, Cho J H, Lee K J, Sung Y C
Department of Life Science, Center for Biofunctional Molecules, School of Environmental Engineering, Pohang University of Science and Technology, Korea.
Mol Cells. 1998 Aug 31;8(4):444-51.
The vaccine development for hepatitis C virus (HCV) is highly urgent to prevent non A and non B hepatitis. It was recently shown that the HCV envelope proteins appeared to the key viral antigens to induce protective immunity. To generate immune responses to the HCV envelope proteins on the DNA-based immunization, various envelope gene-containing plasmids were constructed. For efficient expression and secretion of envelope proteins, the signal sequence of each envelope protein was replaced with either herpes simplex virus type-1 (HSV-1) gD or signal sequence of gD and truncated C-terminal hydrophobic regions of envelope proteins. The intramuscular injection of these plasmids generated a significant level of antibody titers to the E1 and E2 proteins, which maximally reached 850 and 25,000 respectively. The secreted form of each envelope protein and the fusion of the highly immunogenic gD proteins were shown to have no significant effect on generating immune responses to the envelope proteins. In addition, immunized rats appeared to generate antibodies directed to the homologous HVR-1 peptide. Splenic lymphocytes from immunized rats were shown to induce significant T-cell proliferative responses with the stimulation of recombinant E1 and E2 proteins. Our results demonstrated that the HCV envelope-DNA based immunization could elicit both humoral and cellular immune responses.
开发丙型肝炎病毒（HCV）疫苗对于预防非甲非乙型肝炎极为迫切。最近研究表明，HCV包膜蛋白似乎是诱导保护性免疫的关键病毒抗原。为了通过基于DNA的免疫接种对HCV包膜蛋白产生免疫反应，构建了各种含有包膜基因的质粒。为了实现包膜蛋白的高效表达和分泌，将每种包膜蛋白的信号序列替换为单纯疱疹病毒1型（HSV-1）gD或gD的信号序列，并截短包膜蛋白的C端疏水区域。肌肉注射这些质粒可产生针对E1和E2蛋白的高水平抗体滴度，最高分别达到850和25,000。结果表明，每种包膜蛋白的分泌形式以及高免疫原性gD蛋白的融合对产生针对包膜蛋白的免疫反应没有显著影响。此外，免疫大鼠似乎产生了针对同源HVR-1肽的抗体。免疫大鼠的脾淋巴细胞在重组E1和E2蛋白的刺激下可诱导显著的T细胞增殖反应。我们的结果表明，基于HCV包膜-DNA的免疫接种可引发体液免疫和细胞免疫反应。
