Biomedical Research, Hepatitis C, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana 10600, Cuba.
Biotechnol Appl Biochem. 2010 Jul 9;56(3):111-8. doi: 10.1042/BA20090216.
HCV (hepatitis C virus) infection is among the leading causes of chronic liver disease, but currently there is no vaccine available. Data have accumulated about the importance of targeting different HCV antigens in vaccine candidate preparations. Here, a surface response study to select the optimal ratio of recombinant HCV structural antigens in a vaccine preparation, capable of generating in vivo functional cellular immune response in mice, was performed. The immunogenicity of the selected HCV structural protein mixture (Co-E1-E2) in mice and African green monkeys, after five doses of immunization, was also demonstrated. Specific T-cell proliferative response against HCV structural antigens was induced in vaccinated mice. Moreover, on challenge with recombinant HCV VV (vaccinia virus), all mice controlled the viraemia and 80% were protected. On the other hand, monkeys immunized with Co-E1-E2 developed antibodies, specifically directed to region 412-438 of E2 protein, that include an epitope implicated in HCV neutralization, in addition to a specific proliferative response against HCV Core and E2 proteins. These results indicated that the optimal amount and ratio of HCV recombinant proteins should be taken into account to elicit a successful immune response against HCV and therefore have important implications for vaccine design.
丙型肝炎病毒（HCV）感染是慢性肝病的主要原因之一，但目前尚无可用的疫苗。关于在疫苗候选物制备中针对不同 HCV 抗原的重要性的数据已经积累。在这里，进行了一项表面反应研究，以选择在疫苗制剂中能够在体内诱导功能性细胞免疫应答的最佳 HCV 结构抗原重组比例。还证明了在五剂免疫接种后，选择的 HCV 结构蛋白混合物（Co-E1-E2）在小鼠和非洲绿猴中的免疫原性。接种疫苗的小鼠诱导了针对 HCV 结构抗原的特异性 T 细胞增殖反应。此外，在用重组 HCV VV（牛痘病毒）攻毒时，所有小鼠均控制了病毒血症，其中 80%得到了保护。另一方面，用 Co-E1-E2 免疫的猴子产生了针对 E2 蛋白的 412-438 区域的特异性抗体，这些抗体包括在 HCV 中和中起作用的表位，以及针对 HCV Core 和 E2 蛋白的特异性增殖反应。这些结果表明，应考虑 HCV 重组蛋白的最佳数量和比例，以引发针对 HCV 的成功免疫应答，因此对疫苗设计具有重要意义。
