HEPATITIS-C VIRUS ENVELOPE DNA-BASED IMMUNIZATION ELICITS HUMORAL ANDCELLULAR IMMUNE-RESPONSES

The vaccine development for hepatitis C virus (HCV) is highly urgent t o prevent non A and non B hepatitis, It was recently shown that the HC V envelope proteins appeared to the key viral antigens to induce prote ctive immunity. To generate immune responses to the HCV envelope prote ins on the DNA-based immunization, various envelope gene-containing pl asmids mere constructed. For efficient expression and secretion of env elope proteins, the signal sequence of each envelope protein was repla ced with either herpes simplex virus type-1 (HSV-1) gD or signal seque nce of go and truncated C-terminal hydrophobic regions of envelope pro teins. The intramuscular injection of these plasmids generated a signi ficant level of antibody titers to the El and E2 proteins, which maxim ally reached 850 and 25,000 respectively. The secreted form of each en velope protein and the fusion of the highly immunogenic go proteins me re shown to have no significant effect on generating immune responses to the envelope proteins. in addition, immunized rats appeared to gene rate antibodies directed to the homologous HVR-1 peptide. Splenic lymp hocytes from immunized rats mere shown to induce significant T-cell pr oliferative responses with the stimulation of recombinant E1 and E2 pr oteins. Our results demonstrated that the HCV envelope-DNA based immun ization could elicit both humoral and cellular immune responses.