Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana, 10 600, Cuba.
Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana, 10 600, Cuba.
Vaccine. 2014 Mar 26;32(15):1720-6. doi: 10.1016/j.vaccine.2014.01.046. Epub 2014 Jan 30.
HCV is a worldwide health problem despite the recent advances in the development of more effective therapies. No preventive vaccine is available against this pathogen. However, non-sterilizing immunity has been demonstrated and supports the potential success of HCV vaccines. Induction of cross-neutralizing antibodies and T cell responses targeting several conserved epitopes, have been related to hepatitis C virus (HCV) clearance. Therefore, in this work, the immunogenicity of a preparation (MixprotHC) based on protein variants of HCV Core, E1, E2 and NS3 was evaluated in mice and monkeys. IgG from MixprotHC immunized mice and monkeys neutralized the infectivity of heterologous HCVcc. Moreover, strong CD4+ and CD8+ T cells proliferative and IFN-γ secretion responses were elicited against HCV proteins. Remarkably, immunization with MixprotHC induced control of viremia in a surrogate challenge model in mice. These results suggest that MixprotHC might constitute an effective immunogen against HCV in humans with potential for reducing the likelihood of immune escape and viral persistence.
丙型肝炎病毒（HCV）是一个全球性的健康问题，尽管近年来在开发更有效的治疗方法方面取得了进展。目前还没有针对这种病原体的预防性疫苗。然而，已经证明了非灭菌性免疫，并支持 HCV 疫苗的潜在成功。针对几个保守表位的交叉中和抗体和 T 细胞反应的诱导，与丙型肝炎病毒（HCV）的清除有关。因此，在这项工作中，评估了基于丙型肝炎病毒核心、E1、E2 和 NS3 蛋白变异体的制剂（MixprotHC）在小鼠和猴子中的免疫原性。MixprotHC 免疫的小鼠和猴子的 IgG 中和了异源 HCVcc 的感染性。此外，针对 HCV 蛋白，还引发了强烈的 CD4+和 CD8+T 细胞增殖和 IFN-γ分泌反应。值得注意的是，MixprotHC 免疫可诱导小鼠替代挑战模型中的病毒血症控制。这些结果表明，MixprotHC 可能构成针对人类 HCV 的有效免疫原，具有降低免疫逃逸和病毒持续存在可能性的潜力。
