Hepatitis C virus envelope DNA-based immunization elicits humoral and cellular immune responses

The vaccine development for hepatitis C virus (HCV) is highly urgent to prevent non A and non B hepatitis. It was recently shown that the HCV envelope proteins appeared to the key viral antigens to induce protective immunity. To generate immune responses to the HCV envelope proteins on the DNA-based immunization, various envelope gene-containing plasmids were constructed. For efficient expression and secretion of envelope proteins, the signal sequence of each envelope protein was replaced with either herpes simplex virus type-1 (HSV-1) gD or signal sequence of gD and truncated C-terminal hydrophobic regions of envelope proteins. The intramuscular injection of these plasmids generated a significant level of antibody titers to the E1 and E2 proteins, which maximally reached 850 and 25,000 respectively. The secreted form of each envelope protein and the fusion of the highly immunogenic gD proteins were shown to have no significant effect on generating immune responses to the envelope proteins. In addition, immunized rats appeared to generate antibodies directed to the homologous HVR-1 peptide. Splenic lymphocytes from immunized rats were shown to induce significant T-cell proliferative responses with the stimulation of recombinant E1 and E2 proteins. Our results demonstrated that the HCV envelope-DNA based immunization could elicit both humoral and cellular immune responses.