Development of a multigenic plasmid vector for HCV DNA immunization

HCV viral nucleocapsid protein (C), non-structural protein 3 (NS3) and the envelope glycoproteins El and E2 are candidate immune targets for developin g anti-HCV DNA vaccine. Nevertheless, the immune response elicited by these antigens often appears weak and/or transient. Different approaches have be en studied for enhancing and/or modulating the immune response of the DNA v accine. On the basis of a prototype multigenic plasmid vector constituted of two di fferent transcription cassettes (pRC100), we have developed a plasmid vecto r that allows the independent and simultaneous expression of murine IL2 and of an antigenic domain of the HCV NS3 C terminus (pRC112-HCV). The highly conserved NS3 region spans from nt 4403 to nt 4829 and contains two putativ e B and T epitopes. The development of this multigenic plasmid vector may c ombine the expression and local production of an immunomodulatory molecule (mIL2) together with the possibility of addressing the host immune response to the most immunogenic and conserved epitopes, specifically tailored in t he plasmid vector.