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Discovery and structural characterization of a therapeutic antibody against coxsackievirus A10

  • Author(s): Zhu, R
  • Xu, L
  • Zheng, Q
  • Cui, Y
  • Li, S
  • He, M
  • Yin, Z
  • Liu, D
  • Li, S
  • Li, Z
  • Chen, Z
  • Yu, H
  • Que, Y
  • Liu, C
  • Kong, Z
  • Zhang, J
  • Baker, TS
  • Yan, X
  • Hong Zhou, Z
  • Cheng, T
  • Xia, N
  • et al.
Abstract

Copyright © 2018 The Authors. Coxsackievirus A10 (CVA10) recently emerged as a major pathogen of hand, foot, and mouth disease and herpangina in children worldwide, and lack of a vaccine or a cure against CVA10 infections has made therapeutic antibody identification a public health priority. By targeting a local isolate, CVA10-FJ-01, we obtained a potent antibody, 2G8, against all three capsid forms of CVA10. We show that 2G8 exhibited both 100% preventive and 100% therapeutic efficacy against CVA10 infection in mice. Comparisons of the near-atomic cryo-electron microscopy structures of the three forms of CVA10 capsid and their complexes with 2G8 Fab reveal that a single Fab binds a border region across the three capsid proteins (VP1 to VP3) and explain 2G8's remarkable cross-reactivities against all three capsid forms. The atomic structures of this first neutralizing antibody of CVA10 should inform strategies for designing vaccines and therapeutics against CVA10 infections.

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