Recombinant AAV vaccine expressing PEDV S1 enhances immunity with superior neonatal protection

To address suboptimal antibody induction by commercial PEDV vaccines, we constructed a recombinant adeno-associated virus (rAAV-CMV-PEDV S1) expressing regions of the PEDV S1 subunit based on Adeno-associated virus serotype 2 (AAV-2) vector. In mice, rAAV-CMV-PEDV S1 induced significantly more remarkable and persistent serum-specific IgG compared with the inactivated vaccine and accompanied by robust CD3+CD8+ T cells activation within 4 weeks post-immunization. In pregnant sows, compared with commercially available inactivated and attenuated vaccines, the rAAV-CMV-PEDV S1 induced significantly higher serum and colostral IgG as well as neutralizing antibody titers, which provided piglets with abundant maternal antibodies. Crucially, challenge experiments demonstrated that rAAV-CMV-PEDV S1 conferred 80% clinical protective efficacy for piglets, accompanied by significantly reduced viral shedding loads, surpassing other vaccine groups. These findings suggest that rAAV-CMV-PEDV S1 candidate could be a promising PEDV vaccine for enhancing antibody levels and could strengthen the protection of piglets against PEDV infection.