Porcine epidemic diarrhea (PED) is a highly contagious intestinal infectious disease caused by porcine epidemic diarrhea virus (PEDV), which is characterized by a high mortality rate in piglets. Since 2012, a remarkable growth in PED outbreaks occurred in many pig farms in China, landing a heavy blow on the pig industry. In order to develop a new effective vaccine for the current PEDV, oral vaccines were generated by transferring eukaryotic expression recombinant plasmids carrying the S and S (antigenic sites of the S protein) epitopes of PEDV into a swine-origin Lactobacillus acidophilus (L. acidophilus). After oral immunization of the BALB/c mice, higher levels of anti-PEDV specific IgG and SIgA antibodies and cellular immune responses were detected in mice orally administered with the recombinant L. acidophilus-S compared to the L. acidophilus-S. Furthermore, L. acidophilus-S was used to inoculate the pregnant sows orally and the results showed that the recombinant L. acidophilus-S could elicit a specific systemic and mucosal immune response. In summary, our study demonstrated that oral immunization with L. acidophilus-S could improve the humoral and mucosal immune levels in sows and would be a promising candidate vaccine against PEDV infection in piglets.