Basic study for the development of human monoclonal antibodies treating botulism

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Kanazawa University
• Principal Investigator: Matsumura Takuhiro 金沢大学, 医学系, 准教授 (00456930)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ボツリヌス毒素 / ボツリヌス症 / 神経毒素 / ヒト型抗体 / 中和抗体 / 抗毒素製剤

Outline of Final Research Achievements

Botulinum neurotoxin (BoNT) is the most potent natural toxin known. Of the seven BoNT serotypes (A to G), types A, B, E, and F cause human botulism. Treatment of human botulism requires the development of effective toxin-neutralizing antibodies without side effects. In this study, we analyzed the function of human monoclonal antibodies (HuMAbs) neutralizing type B botulinum neurotoxin (BoNT/B), and revealed the mechanisms of action of these HuMAbs. On the other hand, we analyzed the binding and neutralization activity of HuMAbs against type A BoNT (BoNT/A). These HuMAbs recognized non-overlapping epitopes. Furthermore, these HuMAbs showed neutralization activity against BoNT/A individually and three combination of HuMAbs showed a synergistic neutralization effect. These data demonstrate that these HuMAbs against BoNT/B and BoNT/A are promising in terms of a foundation for new human therapeutics for botulism.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

本研究では、当研究室において開発したB型ボツリヌス毒素を中和するヒト型抗体2種の作用機序を明らかにした。本結果より、少ない抗体数で効率よく毒素を中和することのできる機構の一端が明らかとなり、今後新しい抗体を開発する際の重要な知見となった。さらにA型ボツリヌス毒素を認識するヒト型抗体3種の結合および中和活性を解析し、最も高い中和活性を示す組合せを決定した。本研究成果によりA型B型毒素に対する抗体セット候補が得られた。今後はヒトに中毒を起こすE型F型についても本研究で得られた知見を参考に抗体を開発し、ウマ抗毒素に替わる安全で生産効率の優れたヒト型抗ボツリヌス毒素抗体セットの開発に繋げたい。