| Project/Area Number |
13670301
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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 |
Virology
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| Research Institution | Oita University |
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Principal Investigator |
NISHIZONO Akira Oita University, Faculty of Medicine, Professor, 医学部, 教授 (70218155)
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| Co-Investigator(Kenkyū-buntansha) |
SONODA Kengo The Chemo-Sero-Terapeutic Research Institute, Researcher, 第2研究室, 研究員
MNANNEN Kazuaki Oita University, Institute of Scientific Research, Assistant Professor, 医学部・総合科学研究支援センター, 助教授 (20145361)
YAMASHIRO Tetsu Oita University, Institute of Scientific Research, Assistant Professor, 医学部・総合科学研究支援センター, 助教授 (00244335)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Helicobcter pylori / outer membrane virulent gene / Omp gene / cytokine / vaccine / IFN-gamma / CTLA-4 |
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| Research Abstract |
To construct new antigen delivery system, we aimed to develop a recombinant Helicobacter pylori (H. pylori) deleted virulent genes as a candidate for vaccine vector. Further, we analyzed an immune response against H. pylori infection or vaccination of H. pylori antigen for the analysis of live recombinant H. pylori vaccine.
Firstly, we selected H. pylori Omp29 gene as foreign gene acceptor for recombinant H. pylori vaccine vector and achieved to construct H. pylori SS1 strain having GFP gene. The Omp29 gene corresponding fragments were categorized into a ca. 770-bp-long group and a larger fragment group. Sequence analysis indicated that the larger fragments were likely synthesized from the 770-bp fragment by insertion of an irrelevant fragment via 17-bp-long repeat sequences. We postulate that the H. pylori outer membrane protein Omp29 can alter its antigenicity though gene modification mediated by nucleotide transfer.
Next, we studied gastric inflammation and T cell response in H. pylori-infected mice following an intraperioneal immunization using H. pylori antigen. Intraperitoneal immunization by H. pylori antigen inhibited the development of H. pylori-associated gastritis and induced T cell hyporesponsiveness to H. pylori infection, which might be mediated by the early induction of CTLA-4 following challenge infection. Moreover, the predominance of Th2 response by CTLA-4 blockade leads to an inhibition of the development of gastric inflammation. CTLA-4 signaling could contribute to the regulation of Th subsets and the development of gastric inflammation in H. pylori infection.
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