Development of prophylaxis and therapy in norovirus infection with artificial antibodies

• Project/Area Number: 26461516
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Fujita Health University
• Principal Investigator: Moriguchi Kyoko 藤田医科大学, 医学部, 講師 (60298528)
• Project Period (FY): 2014-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 人工抗体 / 受動免疫 / 抗ノロウイルス抗体 / 中和抗体 / ヒト型抗ノロウイルス中和交代 / ファージ交代 / 組織・血液型抗原 / 交差反応性 / ヒト型ファージ抗体 / 抗HuNoVファージ抗体 / 抗HuNoV中和抗体 / ヒトノロウイルス / ヒト型抗ノロウイルスファージ抗体 / ファージ抗体 / ノロウイルスワクチン / 抗原エピトープ / ヒト型抗ノロウイルス抗体 / 組織-血液型抗原 / ヒト型抗体

Outline of Final Research Achievements

The 46 clones of anti-Narita 104 strain (GII.4) and anti-Chiba 407 strain (GI.4) phage antibody were isolated by the phage display method, and 4 clones among them were cross-reactive antibody (GI Internal cross-reactivity 1 clone, GII internal cross-reactivity 2 clones, and GI-GII cross-reactivity 1 clone), and virus particle adsorption inhibitory activity on tissue / blood group antigens that are HuNoV receptor candidate molecules was confirmed to have. In addition, it was confirmed that 25 GII.4-specific antibodies other than these 4 clones also have virus adsorption inhibitory activity on tissue / blood group antigens.

Academic Significance and Societal Importance of the Research Achievements

ノロウイルス感染症は冬季下痢症原因の第一位となっており、高齢者施設や学校、食堂での集団感染事例も多く、大きな社会被害をもたらすが、現在、有効な抗ウイルス薬やワクチンの開発は研究途上にある。健常人であれは予後は良いものの、ウイルスの感染力は強く、高齢者施設での発生は死亡者を出すこともあり、また、ひとたび院内感染が起きると、免疫抑制状態にある患者に慢性的な症状を引き起こすため、その対策が急がれている。このような状況下、中和活性のある抗ノロウイルス人工抗体を開発することは、ヒト血清につきまとう感染因子混入の危険性や倫理面の問題を回避しつつ受動免疫治療を可能にするため、意義のある研究である。

Research Products

• [Journal Article] Detection of norovirus-like particles with an external-force-assisted near-field illumination biosensor (2019)
  • Author(s): Masato Yasuura, Haruko Shirato, Kyoko Higo-Moriguchi, Makoto Fujimaki
  • Journal Title: Japanese Journal of Applied Physics Volume: 58 Issue: 7 Pages: 071005-071005
  • DOI: 10.7567/1347-4065/ab29e2
  • NAID: 210000156402
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors (2017)
  • Author(s): T. Kawahara, Y. Makizaki, Y. Oikawa, Y. Tanaka, A. Maeda, M. Shimakawa, S. Komoto, K. Moriguchi, H. Ohno, K. Taniguchi
  • Journal Title: PLOS one Volume: 27 Pages: 1-22
  • Peer Reviewed / Open Access
• [Journal Article] Chicken egg yolk abtibodies (IgY) for prophylaxis and treatment of rotavirus diarrhea in human and animal neonates: A concise review (2017)
  • Author(s): H. M. Thu, T. W. Myat, M. M. Win, K. Z. Thant, S. Rahman, K. Umeda, S. V. Nguyen, F. C. Icatlo, Jr, K. Higo-Moriguchi, K. Taniguchi, T. Tsuji, K. Oguma, S. J. Kim, H. S. Bae, H. J. Choi
  • Journal Title: Korean J. Food Sci. An. Volume: 37(1) Issue: 1 Pages: 1-9
  • DOI: 10.5851/kosfa.2017.37.1.1
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors (2017)
  • Author(s): Kawahara T, Makizaki Y, Oikawa Y, Tanaka Y, Maeda A, Shimakawa M, Komoto S, Moriguchi K, Ohno H, Taniguchi K
  • Journal Title: PLoS One Volume: 12(3) Issue: 3 Pages: 1-22
  • DOI: 10.1371/journal.pone.0173979
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High Prevalence of G12 Human Rotaviruses in Children with Gastroenteritis in Myanmar (2016)
  • Author(s): Ide T, Higo-Moriguchi K, Komoto S, Htun KW, Myint YY, Myat TW, Thant KZ, Thu HM, Win MM, Oo HN, Htut T, Rahman S, Nguyen SV, Umeda K, Oguma K, Tsuji T, Taniguchi K.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 69 Issue: 4 Pages: 326-327
  • DOI: 10.7883/yoken.JJID.2015.267
  • NAID: 130005165482
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Whole genomic analysis of human G12P[6] and G12P[8] rotavirus strains that have emerged in Myanmar. (2015)
  • Author(s): Ide T, Komoto S, Higo-Moriguchi K, Htun KW, Myint YY, Myat TW, Thant KZ, Thu HM, Win MM, Oo HN, Htut T, Wakuda M, Dennis FE, Haga K, Fujii Y, Katayama K, Rahman S, Nguyen SV, Umeda K, Oguma K, Tsuji T, Taniguchi K.
  • Journal Title: PLoS ONE Volume: 10 Issue: 5 Pages: 1-24
  • DOI: 10.1371/journal.pone.0124965
  • Peer Reviewed / Open Access