This study evaluated the efficacy of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine expressing the full-length PEDV spike (S) protein in protecting piglets against PEDV infection. The vaccine was designed to induce robust humoral and cellular immune responses, including both neutralizing antibodies and antigen-specific T cells. In a mouse model, the S mRNA vaccine induced higher levels of neutralizing antibodies and T cell responses compared to a vaccine expressing a multiepitope chimeric spike (Sm) protein. In piglets, the S mRNA vaccine induced significant increases in binding and neutralizing antibodies, as well as enhanced T cell responses. After a live viral challenge, the S mRNA vaccine significantly reduced clinical signs, gross and histological lesions, and viral load in actively immunized piglets. Additionally, the vaccine provided passive protection to neonatal piglets through colostrum from immunized sows, reducing diarrhea and viral shedding. These findings suggest that the PEDV-S mRNA vaccine is a promising candidate for combating PEDV infection, offering both active and passive immunity.This study evaluated the efficacy of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine expressing the full-length PEDV spike (S) protein in protecting piglets against PEDV infection. The vaccine was designed to induce robust humoral and cellular immune responses, including both neutralizing antibodies and antigen-specific T cells. In a mouse model, the S mRNA vaccine induced higher levels of neutralizing antibodies and T cell responses compared to a vaccine expressing a multiepitope chimeric spike (Sm) protein. In piglets, the S mRNA vaccine induced significant increases in binding and neutralizing antibodies, as well as enhanced T cell responses. After a live viral challenge, the S mRNA vaccine significantly reduced clinical signs, gross and histological lesions, and viral load in actively immunized piglets. Additionally, the vaccine provided passive protection to neonatal piglets through colostrum from immunized sows, reducing diarrhea and viral shedding. These findings suggest that the PEDV-S mRNA vaccine is a promising candidate for combating PEDV infection, offering both active and passive immunity.