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Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VH3 and VK3 genes

Author

Listed:
  • Ting-Hui Lin

    (The Scripps Research Institute)

  • Chang-Chun David Lee

    (The Scripps Research Institute)

  • Monica L. Fernández-Quintero

    (The Scripps Research Institute)

  • James A. Ferguson

    (The Scripps Research Institute)

  • Julianna Han

    (The Scripps Research Institute)

  • Xueyong Zhu

    (The Scripps Research Institute)

  • Wenli Yu

    (The Scripps Research Institute)

  • Jenna J. Guthmiller

    (University of Colorado Anschutz Medical Campus)

  • Florian Krammer

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Medical University of Vienna)

  • Patrick C. Wilson

    (Weill Cornell Medicine)

  • Andrew B. Ward

    (The Scripps Research Institute)

  • Ian A. Wilson

    (The Scripps Research Institute)

Abstract

H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their VH and VK genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against H1N1 viruses.

Suggested Citation

  • Ting-Hui Lin & Chang-Chun David Lee & Monica L. Fernández-Quintero & James A. Ferguson & Julianna Han & Xueyong Zhu & Wenli Yu & Jenna J. Guthmiller & Florian Krammer & Patrick C. Wilson & Andrew B. W, 2025. "Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VH3 and VK3 genes," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56496-4
    DOI: 10.1038/s41467-025-56496-4
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    References listed on IDEAS

    as
    1. Jenna J. Guthmiller & Julianna Han & Henry A. Utset & Lei Li & Linda Yu-Ling Lan & Carole Henry & Christopher T. Stamper & Meagan McMahon & George O’Dell & Monica L. Fernández-Quintero & Alec W. Freyn, 2022. "Broadly neutralizing antibodies target a haemagglutinin anchor epitope," Nature, Nature, vol. 602(7896), pages 314-320, February.
    2. Ying Fu & Zhen Zhang & Jared Sheehan & Yuval Avnir & Callie Ridenour & Thomas Sachnik & Jiusong Sun & M. Jaber Hossain & Li-Mei Chen & Quan Zhu & Ruben O. Donis & Wayne A. Marasco, 2016. "A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
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