A Novel Neutralizing Antibody Targeting a Conserved Conformational Epitope in PDCoV S1 Protein and Its Therapeutic Efficacy in Piglets

On January 22, 2025, a research team led by Prof. Xiaobo Huang from the Research Center for Swine Diseases published a study titled“A Novel Neutralizing Antibody Recognizing a Conserved Conformational Epitope in PDCoV S1 Protein and Its Therapeutic Efficacy in Piglets”in the authoritative virology journalJournal of Virology. The study identified a novel neutralizing monoclonal antibody (mAb 4A6) targeting a conserved conformational epitope in the PDCoV S1 protein and evaluated its therapeutic effects in PDCoV-infected piglets.

Porcine deltacoronavirus (PDCoV) is an intestinal pathogen with global impacts on swine production and potential public health risks due to its cross-species transmission. To prevent and control PDCoV, the development of effective antiviral therapies is critical. However, few studies have explored the efficacy of neutralizing mAbs against PDCoV. The team generated dozens of mAbs targeting the PDCoV S protein and screened mAb 4A6, which demonstrated strong neutralizing activity. Using phage display technology, molecular docking, and alanine scanning mutagenesis, the conformational epitope recognized by mAb 4A6 was mapped.

Figure 2: Identification of critical residues involved in mAb 4A6 binding.

The broad-spectrum antiviral activity of mAb 4A6 was evaluated by indirect ELISA, surface plasmon resonance (SPR) and plaque reduction neutralization tests (PRNT). Results showed that mAb 4A6 exhibited similar binding affinity to representative PDCoV strains from diverse regions, including USA-Ohio137-2014 (North America), CHN-SC2015 (China), and Thailand-S5011-2015 (Southeast Asia). PRNT further confirmed that mAb 4A6 neutralized PDCoV strains isolated over multiple years (CHN-SC2015, SCNC201705, and CHN-SCMY2021-01) with comparable efficacy. These findings indicate that mAb 4A6 possesses broad-spectrum neutralizing activity and consistent affinity across PDCoV strains.

Figure 3: Assessment of mAb 4A6’s binding affinity and neutralizing capacity.

The therapeutic efficacy of mAb 4A6 was evaluated in a PDCoV-infected piglet model. mAb 4A6 delayed disease onset, reduced diarrhea severity, and significantly decreased viral shedding in feces, demonstrating its clinical effectiveness in treating PDCoV-infected piglets.

Figure 4: Therapeutic effects of mAb 4A6 in PDCoV-infected piglets.

In summary, the development of mAb 4A6 and the characterization of its epitope provide critical insights for PDCoV pathogenesis research, novel vaccine design, and antiviral drug development. This neutralizing antibody holds significant clinical potential for PDCoV prevention and control.

Funding:

This study was supported by the Major Science and Technology Project of Yunnan Province (No. 202102AE090039), theBiohazard Prevention and Control Fund of Chenghua Pig Protection Base (No. ZZSS-2024-193),the Sichuan Science and Technology Program (No. 2021ZDZX0010),and theInnovation and Demonstration of Industry and Education Integration in Feed Industrial Chain Transformation and Upgradation, Sichuan Province, China.

Article Link:https://journals.asm.org/doi/10.1128/jvi.02025-24