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.

中文翻译：

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具有非重叠中和位点的针对柯萨奇病毒 A16 的抗体的鉴定。

手足口病是一种常见的儿童疾病，主要由柯萨奇病毒 A16 (CVA16) 引起，目前尚无疫苗或治疗方法。我们鉴定了三种具有治疗潜力的 CVA16 特异性中和单克隆抗体 (nAb)：18A7、14B10 和 NA9D7。我们展示了这些 nAb 与所有三种病毒颗粒形式（成熟病毒颗粒、A 颗粒和空颗粒）结合的原子结构，并表明每个 Fab 可以同时占据成熟病毒颗粒。此外，14B10 或 NA9D7 在新生小鼠模型中提供 100% 的针对致命 CVA16 感染的保护。18A7 与所有三个颗粒中存在的非保守表位结合，而 14B10 和 NA9D7 识别广泛的保护性表位，但仅结合成熟病毒体。NA9D7 靶向免疫显性位点，该位点可能与受体结合位点重叠。这些发现表明 CVA16 疫苗应基于成熟的病毒颗粒，并且这些抗体可用于区分最佳的基于病毒颗粒的免疫原。