Immunogenicity of envelope protein of hepatitis C virus and development of preventive or therapeutical material
| Project/Area Number |
10670465
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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 | Nagoya Institute of Technology |
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Principal Investigator |
NAKANO Isao Nagoya Institute of Technology, Health Adoministration Center Administration Center Associated Professor, 保健管理センター, 助教授 (30262942)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUDA Yoshihide Nagoya Univ., School of Medicine 2<@D1nd@>D1 Dep. Int. Med., Assitant Professor, 医学部・第二内科, 講師 (40181284)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | Hepatitis C virus / DNA based vaccine / Conformational epitope / Anti-E2 antibody / Immunofluorescence study / 中和抗体 / 細胞性免疫 / 免疫蛍光染色 |
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| Research Abstract |
The prevalence of anti-E2 antibody in patients chronically infected with hepatitis C virus (HCV) is reportedly high irrespective of viral genotype, and this cross-reactive antibody if thought to react with a conformational epitope. To investigate the characteristics of this anti-E2 antibody, we measured the immunoreactivity of sera from HCV-1b-infected patients against various modified forms of E2 glycoprotein derived from HCV-H (genotype 1a), using an immunofluorescence technique. Twelve patients of 18 (67%) were positive for anti-E2 antibody, and 10 of these 12 patients required a minimal amino acid region including amino acids (aa) 406 to 644 for strong reactivity, suggesting that the major anti-E2 antibody has a conformational epitope in this region. Subsequent analysis using mutant E2 glycoproteins designed to lose N-glycosylation potential at varying sites revealed seven important N-glycosylation sites in this region. In particular, four of them (aa423, aa430, aa448, and aa576) are indispensable for an antibody response.
Following investigation of the immunogenicity of HCV DNA vaccine was performed in a mouse model. Plasmid carrying the minimal immunogenic region determined above was used as DNA immunogen. Each mouse was injected of 100 ug plasmid DNA with phosphate buffer solution, and their blood was taken at several times with some intervals. Seroconversion of the mice could be detected in almost all the mice, indicating the super-immunogenicity of the DNA vaccine. This may be a candidate of HCV vaccine that is not yet established now.
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Report
(3 results)
Research Products
(3 results)
