Neutralizing antibody levels as a key factor in determining the immunogenic efficacy of the novel PEDV alpha coronavirus vaccine

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.