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Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A viruses

Author

Listed:
  • Wayne D. Harshbarger

    (Dana-Farber Cancer Institute)

  • Derrick Deming

    (Dana-Farber Cancer Institute)

  • Gordon J. Lockbaum

    (University of Massachusetts Medical School)

  • Nattapol Attatippaholkun

    (Dana-Farber Cancer Institute)

  • Maliwan Kamkaew

    (Dana-Farber Cancer Institute)

  • Shurong Hou

    (University of Massachusetts Medical School)

  • Mohan Somasundaran

    (University of Massachusetts Medical School)

  • Jennifer P. Wang

    (University of Massachusetts Medical School)

  • Robert W. Finberg

    (University of Massachusetts Medical School)

  • Quan Karen Zhu

    (Dana-Farber Cancer Institute)

  • Celia A. Schiffer

    (University of Massachusetts Medical School)

  • Wayne A. Marasco

    (Dana-Farber Cancer Institute
    Harvard Medical School)

Abstract

Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among VH3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of VH3-30 antibodies and reveals that 3I14 represents a novel structural solution within the VH3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.

Suggested Citation

  • Wayne D. Harshbarger & Derrick Deming & Gordon J. Lockbaum & Nattapol Attatippaholkun & Maliwan Kamkaew & Shurong Hou & Mohan Somasundaran & Jennifer P. Wang & Robert W. Finberg & Quan Karen Zhu & Cel, 2021. "Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A viruses," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20879-6
    DOI: 10.1038/s41467-020-20879-6
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