Porcine delta-coronavirus (PDCoV) spillovers were recently detected in febrile children, underscoring the recurrent zoonoses of divergent CoVs. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated PDCoV spike (S)-directed monoclonal antibodies (mAbs) from humanized mice and found that two, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryoelectron microscopy (cryo-EM) structures of PD33 and PD41 in complex with the S receptor-binding domain (RBD) and ectodomain trimer revealed the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs competitively interfere with host aminopeptidase N binding to neutralize PDCoV and used deep-mutational scanning epitope mapping to associate RBD antigenic sites with mAb-mediated neutralization potency. Our results indicate a PD33-PD41 mAb cocktail may heighten the barrier to escape. PD33 and PD41 are candidates for clinical advancement against future PDCoV outbreaks.

中文翻译：

---

针对新出现的 delta 冠状病毒的广泛中和抗体的分离和逃逸定位


最近在发热儿童中检测到猪 delta 冠状病毒 （PDCoV） 溢出，突显了不同冠状病毒的反复人畜共患病。迄今为止，还没有疫苗或特异性疗法被批准用于人类对抗 PDCoV。为了为未来可能的 PDCoV 流行做好准备，我们从人源化小鼠中分离出 PDCoV 刺突 （S） 导向的单克隆抗体 （mAb），发现两种命名为 PD33 和 PD41 的抗体广泛中和了一组 PDCoV 变体。PD33 和 PD41 与 S 受体结合结构域 （RBD） 和胞外结构域三聚体复合的冷冻电子显微镜 （cryo-EM） 结构揭示了这些 mAb 识别的表位，使它们的广泛抑制活性合理化。我们表明，两种 mAb 竞争性干扰宿主氨肽酶 N 结合以中和 PDCoV，并使用深度突变扫描表位定位将 RBD 抗原位点与 mAb 介导的中和效力相关联。我们的结果表明，PD33-PD41 mAb 混合物可能会增强逃逸障碍。PD33 和 PD41 是针对未来 PDCoV 爆发的临床进展候选者。