Zika virus (ZIKV) has become a global public health concern because it causes fetal microcephaly and other neurological complications in humans. Currently, there are no approved treatments or vaccines for ZIKV infection. We describe here the epitopes for six monoclonal antibodies (mAbs) that bind to domain III of the envelope protein of ZIKV, some of which have therapeutic potential. We show that by using hydrogen–deuterium exchange mass spectrometry (HDX‐MS), we can identify three spatially distinct epitopes for the six mAbs investigated. The HDX‐MS approach identified epitopes for three mAbs that agreed well with previously reported X‐ray crystallography data. The HDX‐MS determined epitopes for the other three anti‐ZIKV mAbs, for which there were no crystal structures, and the epitopes were confirmed by structure‐guided mutagenesis and biolayer interferometry competition binding assay. Our results have implications for the design of vaccine and antibody therapeutics against ZIKV and demonstrate the use of HDX‐MS as a rapid and valid approach for epitope mapping.

中文翻译：

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氢-氘交换质谱法鉴定寨卡病毒包膜蛋白结构域 III 上空间上不同的抗体表位

寨卡病毒 (ZIKV) 已成为全球公共卫生问题，因为它会导致人类胎儿小头畸形和其他神经系统并发症。目前，尚无批准的 ZIKV 感染治疗方法或疫苗。我们在此描述了与 ZIKV 包膜蛋白结构域 III 结合的六种单克隆抗体 (mAb) 的表位，其中一些具有治疗潜力。我们表明，通过使用氢-氘交换质谱 (HDX-MS)，我们可以确定所研究的六种 mAb 的三个空间上不同的表位。HDX-MS 方法确定了三种 mAb 的表位，这些表位与先前报道的 X 射线晶体学数据一致。HDX-MS 确定了其他三种抗 ZIKV 单克隆抗体的表位，它们没有晶体结构，并通过结构引导诱变和生物层干涉竞争结合测定法确认表位。我们的研究结果对针对 ZIKV 的疫苗和抗体疗法的设计具有重要意义，并证明了 HDX-MS 可作为一种快速有效的表位定位方法。