Oral or nasal immunization of piglets with porcine epidemic diarrhea virus (PEDV) S1 protein bacterial-like particles induces robust intestinal mucosal immune responses and provides reliable protection.

Mucosal immunity, as a key defense mechanism against PEDV infection, has attracted increasing attention. In order to explore the mucosal immunity induced by bacterial-like particles displaying PEDV S1 protein (S1-BLPs), we compared systemic and intestinal immune responses in mice and piglets following intranasal and oral immunization. The nasal or oral administration of S1-BLPs significantly provoked the production of specific IgG and IgA antibodies in the serum (P < 0.05), without difference between the two immunization groups (P > 0.05). Meanwhile, specific IgA antibodies were detected in the small intestinal lavage fluid of mice after booster immunization, but not in the bronchoalveolar lavage fluid. Moreover, the intranasal and oral vaccination of S1-BLPs elevated IFN-γ levels while only IL-2 in oral inoculation in serum of mice. In piglets, after nasal or oral administration of S1-BLPs, specific IgA antibodies were generated in the saliva, nasal mucus and intestinal contents, with an upward trend following booster immunization. Specific IgG and neutralizing antibodies presented in the serum at the same time. After challenge, compared with the challenge control, the immunized piglets exhibited a lower rate of virus shedding, more intact morphology of small intestinal villi, and abundant IgA antibody-secreting cells (ASCs) in the duodenum and jejunum, as well as enhanced lymphocyte proliferation activity of Peyer's patches (PPs). In conclusion, both oral and nasal administration of S1-BLPs stimulate a robust mucosal immune response and provide a reliable immune protection in piglets, indicating that S1-BLPs have great potential to serve as a potential mucosal vaccine for preventing PEDV.