Affinity maturation and property changes of single-domain antibodies through repeated immunizations.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Akazawa Yoko 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (50549897)
• Co-Investigator(Kenkyū-buntansha): 松田 知成 京都大学, 工学研究科, 准教授 (50273488) ; 萩原 義久 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究部門長 (50357761)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 抗体 / 抗原結合能 / 熱安定性

Outline of Final Research Achievements

To efficiently obtain camelid-derived single-domain (VHH) antibodies, we have developed an "antibody sequence evolution tracking method" that combines antigen immunization of alpacas with next-generation sequencing analysis. In this study, we immunized alpacas with antigen multiple times and performed a lepatore analysis of VHH antibody sequences over time. As a result of analyzing the physical properties (antigen-binding capacity and thermal stability) of a cluster of VHH antibodies selected by this screening method, we found that antigen-binding capacity increased with antibody maturation due to immune stimulation, while thermal stability showed a decreasing trend. This "antibody sequence evolution tracking method" can be utilized to predict VHH antibodies that bind to antigens and their physical properties, and is expected to lead to the development of VHH antibodies for therapeutic and diagnostic drugs and materials.

Free Research Field

抗体工学

Academic Significance and Societal Importance of the Research Achievements

抗体蛋白質において、免疫過程の体細胞変異によるアミノ酸配列の変化に伴って抗原との結合がどのように変化しているかを物性解析により明らかにすることで、抗体産生における生物の巧妙な戦略を理解でき、さらに抗体医薬開発の基礎的な知見になり得る。