A computational structural study on recognition of the influenza virus hemagglutinin by hterosubtypic monoclonal antibody

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K08069
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: Igarashi Manabu 北海道大学, 人獣共通感染症国際共同研究所, 准教授 (10374240)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: インフルエンザウイルス / 抗体 / 分子動力学 / 分子モデリング / 分子間相互作用 / 結合自由エネルギー

Outline of Final Research Achievements

We are aiming to design a neutralizing antibody against escape mutant strains and/or multiple HA subtypes of influenza A viruses. In this study, we tried to modify the binding ability of S139/1, a cross-reactive neutralizing monoclonal antibody against HAs, using the binding free energy obtained from molecular dynamics simulations as an indicator. For the HA from A/Victoria/3/75 (H3N2) used in this study, only amino acid substitutions on S139/1 was unable to restore the recogniton ability of S139/1 against escape mutants, suggesting that the replacement of an entire CDR loop are required.

Free Research Field

計算構造生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の最終目的は、抗体の親和性・特異性を制御するための論理的分子設計手法の確立である。このような立体構造を基盤に既存抗体の親和性・特異性を改変する技術は、様々な人獣共通感染症の診断・治療研究へ幅広く応用されることが想定される。本課題の成果はその設計手法の一助となると考えられる。