| Project/Area Number |
16591064
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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 |
Pediatrics
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| Research Institution | Fujita Health University |
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Principal Investigator |
MORIGUCHI Kyoko FUJITA HEALTH UNIVERSITY, School of Medicine, Lecturer, 医学部, 講師 (60298528)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Koki FUJITA HEALTH UNIVERSITY, School of Medicine, Professor, 医学部, 教授 (40094213)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | human rotavirus / cross-reactive / human neutralizing antibodies / VP4 / VP7 / neutralizing epitopes / Abs expression in L.lactis / passive immunization / ヒトロタウイルス(HRV) / 交叉反応性 / ヒト型モノクローナル抗体 / 乳酸菌 / ファージディスプレイ / 交叉応性 / ヒト型モノクローナル中和抗体 |
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| Research Abstract |
Human rotavirus (HRV) is the major cause of severe acute gastroenteritis among infants and children. Vaccination would be the most effective and convenient way to reduce severe HRV gastroenteritis, and some vaccines have recently completed clinical trials. But for immunocompromised patients including adults, vaccination could not be employed. In such case, passive immunity would be an alternative way for prophylaxis or therapy. The human antibody (Ab) library constructed by utilizing a phage-display system was subjected to isolation of neutralizing monoclonal antibodies (N-mAbs) against HRV. Twelve different clones were isolated. Based on the amino acid sequences of variable region of the heavy chain, three representative clones, 1-2H,2-3E, and 2-11Q were characterized, and were found to be cross-reactive to P[4] and P[8] genotypes, cross-reactive to P[6] and P[8] genotypes, and G1 serotype-specific, respectively. The amino acid resides critical for the three human N-mAbs are different from those identified previously in escape variants against mouse N-mAbs. We also mapped the two amino acid residues recognized by the two cross-reactive N-mAbs onto X-ray crystal structure of VP8^* core from HRV. Passive immunity with the three N-mAbs were effective in immnoconpetent mouse, but not effective in SCID mouse, suggesting that proteolysis of orally administered Abs in digestive system. To avoid the proteoclastic chances, we are trying to express N-mAbs in Lactococcus lactise, which enables expression of Abs in intestine.
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