Discovery and structural characterization of a therapeutic antibody against coxsackievirus A10

作者：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^*; Zhou, Z. Hong^*; Cheng, Tong^*; Xia, Ningshao^*

来源：Science Advances, 2018, 4(9): eaat7459.

DOI：10.1126/sciadv.aat7459

• MOUTH-DISEASE
• NEUTRALIZING ANTIBODIES
• CRYOELECTRON MICROSCOPY
• FOOT
• VIRUS
• HAND
• POLIOVIRUS
• OUTBREAK
• CHINA
• ONYCHOMADESIS

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.

• 出版日期2018-9
• 单位厦门大学