Department of Blood Transfusion, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Arch Virol. 2010 Jul;155(7):1097-105. doi: 10.1007/s00705-010-0692-2. Epub 2010 May 15.
Because no vaccine or effective therapy is available, thousands of people with HCV have died in recent years. Cytotoxic T lymphocytes (CTLs) play a critical role in the host cellular immune response against HCV. CTL epitopes in HCV core protein have been identified and used in vaccine development. T helper epitopes could promote cytokine secretion and antibody production to fight HCV. Tetanus toxin, an immunogen with many T helper epitopes, was once used in HBV therapeutic vaccine design. Here, eukaryotic and prokaryotic expression vectors were constructed to express truncated fragments of tetanus toxin and core genes of HCV. HLAA2.1 transgenic mice were inoculated with a recombinant plasmid vehicle with these two heterogenic gene fragments, and this augmented the titres of antibody against HCV. Antigen-specific lymphocyte proliferation, Th1 and Th2 cytokine levels and the number of lysed cells were markedly increased in the combined immunization group compared to controls. These findings provide new insights into a potential role for T helper epitopes from tetanus toxin combined with protein from the HCV core gene, which has numerous CTL epitopes. This design strategy may aid in the development of new vaccines against HCV.
由于目前尚无疫苗或有效疗法,近年来已有数千名 HCV 患者死亡。细胞毒性 T 淋巴细胞 (CTL) 在宿主针对 HCV 的细胞免疫反应中发挥着关键作用。已鉴定出 HCV 核心蛋白中的 CTL 表位,并将其用于疫苗开发。辅助性 T 细胞表位可以促进细胞因子分泌和抗体产生,从而抵抗 HCV。破伤风毒素是一种具有多种辅助性 T 细胞表位的免疫原,曾用于 HBV 治疗性疫苗的设计。在这里,构建了真核和原核表达载体来表达破伤风毒素的截断片段和 HCV 核心基因。用带有这两个异源基因片段的重组质粒载体接种 HLA-A2.1 转基因小鼠,增强了针对 HCV 的抗体滴度。与对照组相比,联合免疫组的抗原特异性淋巴细胞增殖、Th1 和 Th2 细胞因子水平以及裂解细胞的数量明显增加。这些发现为破伤风毒素的辅助性 T 细胞表位与具有众多 CTL 表位的 HCV 核心基因蛋白的潜在作用提供了新的见解。这种设计策略可能有助于开发针对 HCV 的新型疫苗。