Induction of neutralizing antibodies against hepatitis C virus by a subviral particle-based DNA vaccine

Abstract

Direct-acting antivirals (DAAs) have been introduced for the treatment of hepatitis C virus (HCV); however, there is still no available vaccine for preventing HCV infection. We previously reported on a Japanese encephalitis virus (JEV) subviral particle (SVP)-based vaccine with insertion of the HCV E2 neutralization epitope at three positions (SVP-E2/Tri). In this study, we utilized this SVP platform for DNA immunization. In addition, we explored further sites permitting the insertion of HCV epitopes without impairing viral assembly and secretion to elicit higher titers of neutralizing antibodies, and we identified three new positions for foreign epitope insertion. Successful secretion of SVPs with the insertion of HCV epitopes at five positions (SVP-E2/Pent) was seen from transfected cells. Compared to SVP-E2/Tri, sera from mice immunized with the plasmid expressing SVP-E2/Pent showed more neutralization activity against HCV, and less neutralization activity against JEV, suggesting that the additional insertion of HCV epitopes contributed to the induction of antibodies against the inserted peptide, whereas the neutralizing epitopes against JEV were disrupted. This study provides a potentially effective novel DNA vaccine platform.