2003 Fiscal Year Final Research Report Summary
Induction of cellular immune responses against hepatitis C Virus (HCV) and development of HCV vaccines.
| Project/Area Number |
14570461
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Mie University |
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Principal Investigator |
TAMAKI Shigenori Mie University, Hospitals, Assistant, 医学部附属病院, 助手 (80260602)
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| Project Period (FY) |
2002 – 2003
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| Keywords | HCV / CTL / vaccine / alpha antigen / BCG |
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| Research Abstract |
Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) play important roles in the prevention of viral spread and viral clearance during HCV infection. The results of our study contributed to gain more insights into the pathogenesis of HCV infection and allowed the generation of various vaccines against HCV.
1. Establishment of novel animal model of HCV infection
Mice were intravenously inoculated with recombinant adenovirus encoding HCV structural proteins. Expression of HCV structural proteins in hepatocytes were detected immunohistochemically. These mice developed CD8(+) MHC class I-restricted CTLs against all three HCV structural proteins.
2. Recombinant BCG vaccine against HCV
We assessed the capacity of a novel recombinant vaccine using an attenuated tuberculosis bacillus. Calmette-Guerin bacillus (BCG) as a vaccine vehicle to elicit HCV-specific CTLs. BCG was engineered to express the CTL epitope of HCV-NS5a as a chimeric protein with alpha antigen of mycobacteria. Immunization with this recombinant BCG elicited MHC class I-resricted CD8(+) HCV-NS5a-specific CTLs in mice. Immunized mice showed a substantial reduction in the vaccinia virus titer compared with control mice when the immunized mice were challenged with a recombinant vaccinia virus expressing HCV-NS5a genes.
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