PDCoV S mAb

Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen in pigs that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus relies on its spike (S) protein for cell entry, making it a prime target for neutralizing antibodies. Here we generated and characterized a set of neutralizing antibodies targeting the S protein, shedding light on PDCoV S interdomain crosstalk and its vulnerable sites. Among the four identified antibodies, one targets the S1A domain, causing local and long-range conformational changes, resulting in partial exposure of the S1B domain. The other antibodies bind the S1B domain, disrupting binding to the APN receptor. Notably, the epitopes of these S1B-targeting antibodies are concealed in the prefusion S trimer conformation, highlighting the necessity for conformational changes for effective antibody binding. The binding footprint of one S1B binder entirely overlaps with APN-interacting residues and thus targets a highly conserved epitope. These findings provide critical structural insights into the humoral immune response against the PDCoV S protein, potentially guiding vaccine and therapeutic development for this zoonotic pathogen.

猪δ冠状病毒（Porcine deltacoronavirus, PDCoV）是一种新兴的猪肠道病原体，近期已在人体中检出。尽管存在该人畜共患病隐患，但其抗原结构仍未明确。该病毒依赖其刺突（S）蛋白完成细胞入侵，因此刺突蛋白是中和抗体的核心靶点。本研究制备并表征了一组靶向S蛋白的中和抗体，为解析PDCoV S蛋白的域间串扰及其易感位点提供了新见解。在已鉴定的4株抗体中，1株靶向S1A结构域，可引发局部及远距离构象变化，使S1B结构域部分暴露。其余抗体均结合S1B结构域，通过阻断其与氨肽酶N（APN）受体的结合发挥作用。值得注意的是，这些靶向S1B结构域的抗体其表位在融合前S三聚体构象中处于隐蔽状态，这凸显了构象变化对抗体有效结合的必要性。其中1株S1B结合抗体的结合足迹完全覆盖APN结合残基，因此靶向高度保守的表位。本研究结果为抗PDCoV S蛋白的体液免疫应答提供了关键的结构学见解，有望为该人畜共患病原体的疫苗及治疗药物研发提供指导。