The Functional Evaluation of Dendritic Cell Vaccines Based on Different Hepatitis C Virus Nonstructural Genes

Abstract

Hepatitis C virus (HCV) nonstructural (NS) genes are relatively conserved and play critical roles in cellular immune responses against HCV. The aim of the study was to evaluate the immunogenicity of the different HCV NS genes through transduction of DCs and presentation to T cells. Monocyte-derived DCs from healthy donors were infected with the recombinant adenovirus (Ad) harboring HCV NS3 (AdNS3), NS4 (NS4A and NS4B; AdNS4), NS5 (NS5A and NS5B; AdNS5), NS3/NS4 (AdNS3/NS4), and NS4/NS5 (AdNS4/NS5) genes, and then used to stimulate autologous lymphocytes in vitro. Antigen-specific cellular immune responses were detected by interferon-gamma (IFN-gamma), interleukin 4 (IL-4), and Granzyme B (GrB) enzyme-linked immunospot assays (ELISPOT). DCs expressing different HCV NS genes all induced positive immune responses. Furthermore, DCs transfected with AdNS3/NS4 were superior to DCs infected with AdNS3 or AdNS4 in inducing HCV-specific immunity. The same results were obtained when we compared DCs infected with AdNS4/NS5 to AdNS4 or AdNS5. DCs transduced with NS3/NS4 or NS4/NS5 had similar ability to elicit specific immune responses to HCV.