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Characterization of two non-competing antibodies to influenza H3N2 hemagglutinin stem reveals its evolving antigenicity

Author

Listed:
  • Akshita B. Gopal

    (University of Illinois Urbana-Champaign, Department of Biochemistry)

  • Huibin Lv

    (University of Illinois Urbana-Champaign, Department of Biochemistry
    University of Illinois Urbana-Champaign, Carl R. Woese Institute for Genomic Biology)

  • Tossapol Pholcharee

    (University of Illinois Urbana-Champaign, Department of Biochemistry)

  • Wenhao O. Ouyang

    (University of Illinois Urbana-Champaign, Department of Biochemistry)

  • Qi Wen Teo

    (University of Illinois Urbana-Champaign, Department of Biochemistry
    University of Illinois Urbana-Champaign, Carl R. Woese Institute for Genomic Biology)

  • Yasha Luo

    (Guangdong Women and Children Hospital, Department of Clinical Laboratory)

  • Yun Sang Tang

    (The Chinese University of Hong Kong, The Jockey Club School of Public Health and Primary Care
    The Chinese University of Hong Kong, Li Ka Shing Institute of Health Sciences, Faculty of Medicine)

  • Mingyong Luo

    (Guangdong Women and Children Hospital, Department of Clinical Laboratory)

  • Chris K. P. Mok

    (The Chinese University of Hong Kong, The Jockey Club School of Public Health and Primary Care
    The Chinese University of Hong Kong, Li Ka Shing Institute of Health Sciences, Faculty of Medicine
    The Chinese University of Hong Kong, S.H. Ho Research Centre for Infectious Diseases
    The Chinese University of Hong Kong, School of Biomedical Sciences)

  • Nicholas C. Wu

    (University of Illinois Urbana-Champaign, Department of Biochemistry
    University of Illinois Urbana-Champaign, Carl R. Woese Institute for Genomic Biology
    University of Illinois Urbana-Champaign, Center for Biophysics and Quantitative Biology
    University of Illinois Urbana-Champaign, Carle Illinois College of Medicine)

Abstract

The conserved stem domain of influenza hemagglutinin (HA), which is classified into group 1 and group 2, is a target of broadly neutralizing antibodies. While many group 1 HA stem antibodies have been described, much less is known about group 2 HA stem antibodies. This study structurally characterizes two group 2 HA stem antibodies, 2F02 and AG2-G02, targeting the central stem epitope and the lower stem epitope, respectively. Unlike prototypic antibodies to group 2 HA stem, 2F02 and AG2-G02 do not compete for binding. Both antibodies offer protection in a female mouse model via neutralization activity and Fc-mediated effector functions. We further demonstrate that the natural evolution of HA2 position 32 restricts the binding of AG2-G02 to recent human H3N2 HAs and influences the binding of human plasma samples. Overall, these findings advance our understanding of the antigenicity of HA stem, which has important implications for the development of broadly protective influenza vaccines.

Suggested Citation

  • Akshita B. Gopal & Huibin Lv & Tossapol Pholcharee & Wenhao O. Ouyang & Qi Wen Teo & Yasha Luo & Yun Sang Tang & Mingyong Luo & Chris K. P. Mok & Nicholas C. Wu, 2025. "Characterization of two non-competing antibodies to influenza H3N2 hemagglutinin stem reveals its evolving antigenicity," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65595-1
    DOI: 10.1038/s41467-025-65595-1
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