Induction of cytotoxic lymphocyte response to hepatitis C virus using anthrax toxin-mediated antigen delivery system

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We have investigated the protective antigen (PA) and recombinant lethal factor (LF) expressing epitope of hepatitis C virus (HCV) to induce cytotoxic T lymphocytes (CTL). Fusion protein of LF with epitope of core region (LMGYIPLVGA : #1) induced CTL response comparable with recombinant plasmid DNA encoding the core epitope when immuinzed mice with PA.In addition to #1 epitope, CTL activity was detected in another core epitope (YLLPRRGPRL : #5). These results indicate that antigen delivery system of PALF may be useful as HCV vaccine candidate. In the route screening for immunization among the intramuscle, subcutis and intraperitoneum, intra- muscular route seems to be better. To compare the immunization condition between the J774 A.1, macrophage cell line, pulsed with PALF#1 ex vivo and conventional solution of PALF#1, strong- er CTL response was obtained in the former immunization protocol. When compared the antigen presenting cells, dendritic cells was more efficient to elicite CTL response than the application by J774 A.1. Immunization with PA and LF#1 adsorbed to latex beads elicited strong CTL response. When latex beads were treated with PALF#l together with anti-CD40 and GM-CSF, CTL response was at least 2-fold more efficiently than was PALF#1 latex beads. CTL induced by PALF#1 could kill the targets expressed the epitope endo- geneously after infection of recombinant vaccinia virus expressing core protein. These findings are indicating that application of PA and LF-epitope is an efficient molecular tool to use as CTL vaccine. The findings of this antigen delivery system may give us some useful informations for new approach concerning HCV vaccine development.