DNA vaccination for the induction of immune responses against hepatitis C virus proteins

Recent analysis of clinical and experimental cases of hepatitis C virus (HCV) infection suggest the possible role of the viral nucléocapsid (C), the nonstructural protein 3 (NS3) and the envelope glycoproteins E1 and/or E2 in the mounting of immune responses capable to control infection (Botarelli et al., Gastroenterology, 1993, 104, 580-587; Choo et al., Proc. Natl Acad. Sci. USA, 1994, 91, 1294-1298). We have used DNA-based immunization to study the immune responses that can be induced by injecting DNA-derived immunogens encoding C and E2 sequences. Comparative analysis were performed in mice using expression plasmids containing full-length or partial gene sequences cloned in fusion with the hepatitis B virus surface antigen (HBV-HCV chimeras). The results obtained indicate that: (1) anti-C and anti-E2 antibodies can be induced with all constructs including the HBV-HCV chimeras; (2) titers range from 1:100 to 1:100000 depending on the antigen and nucleotide sequence context; (3) all HCV DNA immunogens are associated with a predominant Th1 response; (4) CTL can be detected against both HCV and HBV determinants.