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Title | Identification of Antibodies with Non-overlapping Neutralization Sites that Target Coxsackievirus A16. |
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Journal, issue, pages | Cell Host Microbe, Vol. 27, Issue 2, Page 249-261.e5, Year 2020 |
Publish date | Feb 12, 2020 |
Authors | Maozhou He / Longfa Xu / Qingbing Zheng / Rui Zhu / Zhichao Yin / Zhenghui Zha / Yu Lin / Lisheng Yang / Yang Huang / Xiangzhong Ye / Shuxuan Li / Wangheng Hou / Yangtao Wu / Jinle Han / Dongxiao Liu / Zekai Li / Zhenqin Chen / Hai Yu / Yuqiong Que / Yingbin Wang / Xiaodong Yan / Jun Zhang / Ying Gu / Z Hong Zhou / Tong Cheng / Shaowei Li / Ningshao Xia / |
PubMed Abstract | Hand, foot, and mouth disease is a common childhood illness primarily caused by coxsackievirus A16 (CVA16), for which there are no current vaccines or treatments. We identify three CVA16-specific ...Hand, foot, and mouth disease is a common childhood illness primarily caused by coxsackievirus A16 (CVA16), for which there are no current vaccines or treatments. We identify three CVA16-specific neutralizing monoclonal antibodies (nAbs) with therapeutic potential: 18A7, 14B10, and NA9D7. We present atomic structures of these nAbs bound to all three viral particle forms-the mature virion, A-particle, and empty particle-and show that each Fab can simultaneously occupy the mature virion. Additionally, 14B10 or NA9D7 provide 100% protection against lethal CVA16 infection in a neonatal mouse model. 18A7 binds to a non-conserved epitope present in all three particles, whereas 14B10 and NA9D7 recognize broad protective epitopes but only bind the mature virion. NA9D7 targets an immunodominant site, which may overlap the receptor-binding site. These findings indicate that CVA16 vaccines should be based on mature virions and that these antibodies could be used to discriminate optimal virion-based immunogens. |
External links | Cell Host Microbe / PubMed:32027857 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.65 - 3.78 Å |
Structure data | EMDB-0887, PDB-6lha: EMDB-0888, PDB-6lhb: EMDB-0889, PDB-6lhc: EMDB-0890, PDB-6lhk: EMDB-0891, PDB-6lhl: EMDB-0892, PDB-6lho: EMDB-0894, PDB-6lhp: EMDB-0895, PDB-6lhq: EMDB-0897, PDB-6lht: EMDB-0898: |
Chemicals | ChemComp-SPH: |
Source |
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Keywords | VIRUS / VIRAL PROTEIN / localized reconstruction |