Poliovirus-derived CTL-inducing Hepatitis C Vaccine by Modification of RPS-Vax with Protein Transduction Domain

ABSTRACT

We have reported RPS-Vax system by introducing multiple cloning site (MCS) and 3C-protease cutting site at the N-terminal end of the poliovirus Sabin 1 cDNA. Potential vaccine genes can be easily introduced into recombinant polioviral genome and expressed during the viral replication as a part of virus polyprotein and subsequently processed from the mature viral protein by the poliovirus-specific 3C-protease. However, these poliovirus vector-mediated chimeric viral vaccine was not efficient to induce the cell-mediated immunity because of its rapid cytolytic capacity. In order to make CTL-inducing vaccine vector, we integrated a protein transduction domain (PTD) into the pRPS-Vax vector system right ahead of the MCS, named RPS-Vax/PTD. We have incorporated the HCV core (N-terminal 100aa) antigen into the MCS of pRPSvax-PTD vector, followed by production of chimeric virus, named RPSvax-PTD/HCVc. The chimeric virus was genetically stable during the serial passages. Replication capacity of the RPSvax-PTD/HCVc was 1~2 log lower than that of RPS-Vax control virus. These chimeric virus was very efficient to inducing antigen-specific IgG2a in the immunized mice, implying that the recombinant virus has a capacity to induce HCV-specific Th1 type immunity in the immunized animals or humans.