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

Research Project

Project/Area Number 11670303
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionSaitama Medical School

Principal Investigator

MORIYA Osamu  SAITAMA MED.SCHOOL, DEPARTMENT OF MICROBIOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (40049862)

Co-Investigator(Kenkyū-buntansha) AKATSUKA Toshitaka  SAITAMA MED.SCHOOL, DEPARTMENT OF MICROBIOLOGY, PROFESSOR, 医学部, 教授 (30159321)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsANTHRAX TOXIN / CTL / HCV / VACCINE / HCV / PA-LF蛋白 / BALB / cマウス / ワクチン
Research Abstract

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.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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