Establishment of antiviral small molecule antibody technology

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20780
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: AKAZAWA Daisuke 国立感染症研究所, 治療薬・ワクチン開発研究センター, 主任研究官 (50953527)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: シングルドメイン抗体 / 抗ウイルス

Outline of Final Research Achievements

Focusing on small molecular antibodies as a new modality that can overcome the weaknesses of existing antibody drugs, we investigated methods for producing and screening diverse clones of single domain antibodies targeting virus-host protein interactions.
(1) We immunized alpacas with recombinant hepatitis virus receptor proteins and confirmed the induction of antigen-specific antibodies. We also established a method for isolating alpaca B cells expressing antigen-binding VHH, and after identifying the VHH antibody sequence, we produced and evaluated recombinant monoclonal VHH antibodies to obtain monoclonal antibodies.
(2) Using a VHH antibody library, we screened VHH antibodies against viral antigens and found that it is possible to generate high-affinity multivalent and bispecific antibodies.

Free Research Field

ウイルス学、生物工学

Academic Significance and Societal Importance of the Research Achievements

抗体は標的特異性および親和性が高く副作用も少ないモダリティであるが、高分子であるため、立体障害により機能性部位にアクセスできない場合があること、製造に多大なコストがかかるなどの課題がある。本研究成果は、これらの課題を解決すべく、低分子抗体に着目して研究を進めてきた。本研究成果は、既存抗体では得られにくい多様性エピトープを有する抗体作製手法や抗体改変技術を含み、新規抗ウイルス薬モダリティの発展に繋がることが期待できる。