DNA VACCINATION FOR THE INDUCTION OF IMMUNE-RESPONSES AGAINST HEPATITIS-C VIRUS PROTEINS

Recent analysis of clinical and experimental cases of hepatitis C viru s (HCV) infection suggest the possible role of the viral nucleocapsid (C), the nonstructural protein 3 (NS3) and the envelope glycoproteins E1 and/or E2 in the mounting of immune responses capable to control in fection (Botarelli et al., Gastroenterology, 1993, 104, 580-587; Choo ct al., Proc. Natl Acad. Sci. USA, 1994, 91, 1294-1298). We have used DNA-based immunization to study the immune responses that can be induc ed by injecting DNA-derived immunogens encoding C and E2 sequences. Co mparative analysis were performed in mice using expression plasmids co ntaining full-length or partial gene sequences cloned in fusion with t he hepatitis B virus surface antigen (HBV-HCV chimeras). The results o btained indicate that: (1) anti-C and anti-E2 antibodies can be induce d with all constructs including the HE V-HCV chimeras; (2) titers rang e from 1:100 to 1:100000 depending on the antigen and nucleotide seque nce context; (3) all HCV DNA immunogens are associated with a predomin ant Th1 response; (4) CTL can be detected against both HCV and HBV det erminants. (C) 1997 Elsevier Science Ltd.