Abstract

Porcine epidemic diarrhea virus (PEDV) remains a major threat to the global swine industry, with genotype II (GII) strains causing nearly 100% mortality in neonatal piglets. Current vaccination strategies and biosafety control measures provide limited cross-protection and may pose potential biosafety risks, highlighting the urgent need for safer and more effective preventive approaches. In this study, we evaluated a spike (S) protein subunit vaccine administered via needle-free intradermal (ID) immunization and assessed its capacity to induce maternally derived passive protection. ID immunization elicited robust PEDV-specific IgG and neutralizing antibody responses comparable to those induced by conventional intramuscular (IM) injection, with immune responses maintained for more than four months. High levels of IgG and neutralizing antibodies were detected in the serum and colostrum of vaccinated sows, and piglets born to these sows exhibited only mild or no diarrhea following virulent PEDV challenge. Viral shedding and intestinal viral loads were markedly reduced, and intestinal lesions were nearly completely prevented. Overall, this needle-free ID vaccination strategy conferred more than 95% passive protection in neonatal piglets while improving animal welfare and vaccination efficiency. These findings demonstrate that ID delivery of an S protein subunit vaccine represents a promising and practical alternative to conventional IM vaccination for effective PEDV control.