Porcine epidemic diarrhea virus (PEDV) causes significant global agricultural losses. Despite commercial inactivated and live attenuated vaccines, persistent outbreaks underscore the need for more effective solutions. Here, we isolated a novel Chinese PEDV variant, PEDV ShXXY2-2023, with amino acid substitutions in key neutralizing epitopes (N-terminal domain, receptor-binding domain, and CO-26K equivalent epitope) compared to vaccine strains. An inactivated ShXXY2-2023 vaccine induced higher neutralizing antibodies and superior cross-protection versus commercial vaccines. Vaccinated sows conferred enhanced protection to offspring, improving piglet survival post-challenge. Maternal serum neutralizing antibody titers correlated strongly with piglet survival; titers of 1:377-1:774 at one week prepartum yielded >80% protective efficacy. These findings emphasize neutralizing antibodies' critical role in PEDV prevention and position ShXXY2-2023 as a promising vaccine candidate, with broader implications for coronavirus vaccine development.
Keywords: Porcine epidemic diarrhea virus; S protein; broad protection; coronavirus; equivalent epitope; mutant strain; neutralizing antibody; vaccines.