Hepatitis C virus Department, Center for Genetic Engineering and Biotechnology, Avenue 31, P.O. Box. 6162, Havana, 610600, Cuba.
Microscopy Department, Center for Genetic Engineering and Biotechnology, Avenue 31, P.O. Box. 6162, Havana, 610600, Cuba.
Arch Virol. 2020 Mar;165(3):593-607. doi: 10.1007/s00705-019-04464-x. Epub 2020 Feb 3.
The eradication of hepatitis C virus (HCV) infection is a public health priority. Despite the efficiency of treatment with direct-acting antivirals, the high cost of the therapy and the lack of accurate data about the HCV-infected population worldwide constitute important factors hampering this task. Hence, an affordable preventive vaccine is still necessary for reducing transmission and the future disease burden globally. In this work, chimeric proteins (EnvCNS3 and NS3EnvCo) encompassing conserved and immunogenic epitopes from the HCV core, E1, E2 and NS3 proteins were produced in Escherichia coli, and their immunogenicity was evaluated in BALB/c mice. The impact of recombinant HCV E2.680 protein and oligodeoxynucleotide 39M (ODN39M) on the immune response to chimeric proteins was also assessed. Immunization with chimeric proteins mixed with E2.680 enhanced the antibody and cellular response against HCV antigens and chimeric proteins. Interestingly, the combination of NS3EnvCo with E2.680 and ODN39M as adjuvant elicited a potent antibody response characterized by an increase in antibodies of the IgG2a subclass against E2.680, NS3 and chimeric proteins, suggesting the induction of a Th1-type response. Moreover, a cytotoxic T lymphocyte response and a broad response of IFN-γ-secreting cells against HCV antigens were induced with this formulation as well. This T cell response was able to protect vaccinated mice against challenge with a surrogate model based on HCV recombinant vaccinia virus. Overall, the vaccine candidate NS3EnvCo/E2.680/ODN39M might constitute an effective immunogen against HCV with potential for reducing the likelihood of viral persistence.
消除丙型肝炎病毒 (HCV) 感染是公共卫生的重点。尽管直接作用抗病毒药物的治疗效果显著，但治疗费用高昂，以及全球 HCV 感染人群缺乏准确数据，这些都是阻碍这一任务的重要因素。因此，仍然需要一种负担得起的预防性疫苗来减少全球的传播和未来疾病负担。在这项工作中，嵌合蛋白（EnvCNS3 和 NS3EnvCo）在大肠杆菌中表达，包含 HCV 核心、E1、E2 和 NS3 蛋白的保守和免疫原性表位，并在 BALB/c 小鼠中评估其免疫原性。还评估了重组 HCV E2.680 蛋白和寡脱氧核苷酸 39M (ODN39M) 对嵌合蛋白免疫反应的影响。用与 E2.680 混合的嵌合蛋白免疫增强了针对 HCV 抗原和嵌合蛋白的抗体和细胞反应。有趣的是，将 NS3EnvCo 与 E2.680 和 ODN39M 联合作为佐剂可引起强烈的抗体反应，表现为针对 E2.680、NS3 和嵌合蛋白的 IgG2a 类抗体增加，表明诱导了 Th1 型反应。此外，该配方还诱导了细胞毒性 T 淋巴细胞反应和 IFN-γ 分泌细胞对 HCV 抗原的广泛反应。这种 T 细胞反应能够保护接种疫苗的小鼠免受基于 HCV 重组痘苗病毒的替代模型的挑战。总体而言，候选疫苗 NS3EnvCo/E2.680/ODN39M 可能是一种有效的 HCV 免疫原，具有降低病毒持续存在可能性的潜力。
