A novel neutralizing antibody recognizing a conserved conformational epitope in PDCoV S1 protein and its therapeutic efficacy in piglets

作者：Rui Chen, Guiping Zhou, Junpeng Yang, Rong Yuan, Ying Sun, Yixiao Liang, Rui Wu, Yiping Wen, Yiping Wang, Qin Zhao, Senyan Du, Qigui Yan, Sanjie Cao, Xiao-Bo Huang · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.02025-24 · 被引用次数：5 · 研究领域：Animal Virus Infections Studies、Viral Infections and Immunology Research、SARS-CoV-2 and COVID-19 Research

Porcine deltacoronavirus (PDCoV) is an enteric pathogen that burdens the global pig industry and is a public health concern. The development of effective antiviral therapies is necessary for the prevention and control of PDCoV, yet to date, there are few studies on the therapeutic potential of PDCoV-neutralizing antibodies. Here, we investigate the therapeutic potential of a novel monoclonal antibody (mAb 4A6) which targets the PDCoV S1 protein and effectively neutralizes PDCoV, both pre- and post-attachment on cells, with IC50 values of 0.537 and 8.487 µg/mL, respectively. A phage-display peptide library was used to determine the epitope recognized by mAb 4A6, and two mimotopes, QYPVSYA (P1) and FPHWPTI (P2), were identified. KLH-P1 reacted with PDCoV-positive sera but failed to induce PDCoV-specific IgG and neutralizing antibodies in mice, suggesting P1 does not fully mimic the conformational epitope. Molecular docking and alanine scanning mutagenesis revealed that S461, P462, T463, E465, and Y467 on the S protein are essential for mAb 4A6 binding. Antibody therapy experiments in PDCoV-infected piglets showed that administering mAb 4A6 once or twice could delay the onset of diarrhea symptoms, reduce the severity of diarrhea, and decrease virus shedding. Taken together, our findings demonstrate that mAb 4A6 holds promise as a treatment against PDCoV, and the amino acids recognized by mAb 4A6 will be valuable for developing novel epitope-based vaccines or antiviral drugs. IMP...