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Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71

Author

Listed:
  • Kuan-Ying A. Huang

    (Chang Gung Memorial Hospital
    Chang Gung University)

  • Daming Zhou

    (University of Oxford)

  • Elizabeth E. Fry

    (University of Oxford)

  • Abhay Kotecha

    (University of Oxford)

  • Peng-Nien Huang

    (Chang Gung University
    Chang Gung University)

  • Shu-Li Yang

    (Chang Gung University
    Chang Gung Memorial Hospital)

  • Kuo-Chien Tsao

    (Chang Gung University
    Chang Gung Memorial Hospital)

  • Yhu-Chering Huang

    (Chang Gung Memorial Hospital)

  • Tzou-Yien Lin

    (Chang Gung Memorial Hospital)

  • Jingshan Ren

    (University of Oxford)

  • David I. Stuart

    (University of Oxford
    Diamond Light Source Ltd)

Abstract

Enterovirus 71 (EV71)-neutralizing antibodies correlate with protection and have potential as therapeutic agents. We isolate and characterize a panel of plasmablast-derived monoclonal antibodies from an infected child whose antibody response focuses on the plateau epitope near the icosahedral 3-fold axes. Eight of a total of 19 antibodies target this epitope and three of these potently neutralize the virus. Representative neutralizing antibodies 38-1-10A and 38-3-11A both confer effective protection against lethal EV71 challenge in hSCARB2-transgenic mice. The cryo-electron microscopy structures of the EV71 virion in complex with Fab fragments of these potent and protective antibodies reveal the details of a conserved epitope formed by residues in the BC and HI loops of VP2 and the BC and HI loops of VP3 spanning the region around the 3-fold axis. Remarkably, the two antibodies interact with the epitope in quite distinct ways. These plateau-binding antibodies provide templates for promising candidate therapeutics.

Suggested Citation

  • Kuan-Ying A. Huang & Daming Zhou & Elizabeth E. Fry & Abhay Kotecha & Peng-Nien Huang & Shu-Li Yang & Kuo-Chien Tsao & Yhu-Chering Huang & Tzou-Yien Lin & Jingshan Ren & David I. Stuart, 2020. "Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19013-3
    DOI: 10.1038/s41467-020-19013-3
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