Vaccine compositions for preventing or treating C hepatitis wherein a protease cleaved HCV site C191 where regulation of activity by prevention of migration of C protein into nucleus and interaction with E1 polypeptide

摘要

A composition for treating or preventing hepatitis C (HCV) induced infections, which in a preferred embodiment, comprising (i) a fusion polypeptide containing; (a) a C polypeptide of the hepatitis C virus (HCV) or a portion thereof that comprises a C polypeptide region responsible for gene regulatory activity; and (b) an E1 envelope polypeptide of the hepatitis C virus or a portion thereof that comprises an E1 polypeptide region responsible for cytoplasmic anchorage of the E1 polypeptide. The two polypeptide portions of (a) and (b) are fused by peptide bond where the bond may not be cleaved by a mammalian protease; or (ii) a fusion polypeptide containing (a) a C polypeptide of HCV or a portion thereof that comprises (1) a first C polypeptide region responsible for gene regulatory activity and (2) a second C polypeptide region responsible for the interaction with the E1 envelope polypeptide; (b) an E1 envelope polypeptide of HCV or a portion thereof that comprises: (1) a first E1 polypeptide region responsible for E1 cytoplasmic anchorage and (2) a second E1 polypeptide region responsible for the interaction with the second C polypeptide region; wherein the C polypeptide is fused by a peptide bond to the E1 envelope polypeptide, and where the C polypeptide comprises Cysteine172-Serine172-Phenylalanine174-Serine175 with at least one mutation between amino acid numbers 172-175; or (iii) a mixture of (a) of a C polypeptide HCV comprising (1) a first C polypeptide region responsible for gene regulatory activity and (2) a second C polypeptide region responsible for the interaction with the E1 envelope polypeptide wherein the C polypeptide comprises Cysteine172-Serine172-Phenylalanine174-Serine175 with at least one mutation between amino acid numbers 172-175 and (b) an envelope polypeptide of HCV comprising (1) a first E1 polypeptide region responsible for E1 cytoplasmic anchorage and (2) a second E1 polypeptide region responsible for the interaction with the second C polypeptide region; or (iv) a DNA molecule comprising a sequence encoding the fusion polypeptide for expression in mammalian cells.