Identification of a novel epitope conserved among influenza A viruses

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07038
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Yamayoshi Seiya 国立研究開発法人国立国際医療研究センター, 研究所, 部長 (50529534)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: インフルエンザ / HA蛋白質 / モノクローナル抗体

Outline of Final Research Achievements

To enhance our understanding of the epitopes recognized by heterosubtypic mAbs, we attempted to identify cross-reactive human mAbs from a panel of mAbs that were previously reported to be specific for H3-HA. We clarified the cross-reactivity of seventy-five mAbs by ELISA and found that clone 4F02 was broadly reactive against all 18 HA subtypes of influenza A viruses. 4F02 neutralized several H3N2 viruses in vitro, showed weak hemagglutination inhibitory activity, inhibited HA-mediated fusion activity, activated the Fc receptor-mediated signaling pathway in effector cells, and protected mice against lethal challenge infection with H1N1pdm09, H3N2, H5N1, and H7N9 viruses. Cryo-EM analysis revealed that 4F02 targeted the base of the HA head. Its epitope consisted of amino acid residues within the antigenic sites C, D, and E, spanning between the HA head and stem. This finding provides novel insight into the development of a universal influenza vaccine.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

全ての亜型のA型インフルエンザウイルスのHA蛋白質を認識するヒトモノクローナル抗体である4F02のエピトープを同定したことにより、HA蛋白質に存在する亜型間で高度に保存されたエピトープを明らかにすることが出来ました。このような保存性の高いエピトープに対する抗体を効率的に誘導するワクチンをデザインすることが出来れば、一つの亜型のインフルエンザウイルスのみならず、様々な亜型のインフルエンザウイルスに対して有効なユニバーサルインフルエンザワクチンとなる可能性があります。