Development of a Mucosal Immune-Enhancing Oral Vaccine Candidate Against Porcine Epidemic Diarrhea Virus Using Lactobacillus paracasei

Porcine epidemic diarrhea virus (PEDV) is a highly infectious virus that leads to severe diarrhea and high death rates in neonatal piglets. Because PEDV primarily infects the intestinal mucosa, the induction of effective mucosal immunity through oral vaccination represents a promising strategy for disease prevention. In this study, a recombinant <i>Lactobacillus paracasei</i> (<i>L. paracasei</i>) strain expressing a multicomponent fusion antigen composed of the PEDV S1 protein, M cell- and dendritic cell-targeting peptides, and the mucosal adjuvant LTB was constructed as a candidate oral vaccine. Pregnant mice orally immunized with the recombinant strain exhibited significantly increased levels of PEDV-specific serum IgG as well as secretory IgA (SIgA) in intestinal mucus and feces, both of which showed in vitro neutralizing activity. In addition, oral immunization markedly enhanced cellular immune responses, as indicated by elevated serum levels of IFN-γ, IL-2, IL-4, and IL-10. Notably, newborn mice delivered by immunized dams displayed significantly higher levels of PEDV-specific SIgA, demonstrating effective maternal antibody transfer. These results indicate that the recombinant <i>L. paracasei</i> strain can robustly induce humoral, cellular, and mucosal immune responses and confer maternal immune protection. This study emphasizes the possibility of oral vaccinations based on <i>L. paracasei</i> as a viable approach to the prevention and management of epidemic diarrhea in piglets.