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Discovery and structural characterization of a therapeutic antibody against coxsackievirus A10.

  • Author(s): Zhu, Rui
  • Xu, Longfa
  • Zheng, Qingbing
  • Cui, Yanxiang
  • Li, Shaowei
  • He, Maozhou
  • Yin, Zhichao
  • Liu, Dongxiao
  • Li, Shuxuan
  • Li, Zizhen
  • Chen, Zhenqin
  • Yu, Hai
  • Que, Yuqiong
  • Liu, Che
  • Kong, Zhibo
  • Zhang, Jun
  • Baker, Timothy S
  • Yan, Xiaodong
  • Hong Zhou, Z
  • Cheng, Tong
  • Xia, Ningshao
  • et al.
Abstract

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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