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

## TL;DR

Researchers developed an oral vaccine using Lactobacillus paracasei to boost mucosal immunity against a deadly pig virus, showing strong immune responses and maternal protection in mice.

## Contribution

A novel oral vaccine candidate using Lactobacillus paracasei expressing a fusion antigen for mucosal immunity against PEDV is developed and tested.

## Key findings

- Oral immunization with the recombinant L. paracasei increased PEDV-specific antibodies in serum and intestinal mucus.
- Newborn mice from immunized mothers showed higher PEDV-specific antibodies, indicating maternal immunity transfer.
- The vaccine enhanced cellular immunity with elevated cytokine levels like IFN-γ, IL-2, IL-4, and IL-10.

## Abstract

Porcine epidemic diarrhea virus (PEDV) is a highly contagious pathogen that infects the intestinal tract of piglets, causing severe diarrhea and high newborn piglet deaths, causing the swine industry to suffer large financial losses. Given that PEDV primarily targets the intestinal mucosa, oral vaccines designed to stimulate mucosal immunity may offer effective protection. In this study, we developed a recombinant strain of Lactobacillus paracasei that expresses a fusion antigen comprising the PEDV S1 protein, immune cell-targeting peptides, and a mucosal adjuvant. Oral immunization of pregnant mice with this recombinant strain resulted in a significant increase in PEDV-specific antibodies in both the bloodstream and intestinal tract, with these antibodies demonstrating the ability to neutralize the virus in vitro. Furthermore, the vaccine enhanced cellular immune responses, evidenced by elevated levels of immune-related cytokines. Notably, newborn mice born to immunized mothers exhibited higher levels of PEDV-specific antibodies, indicating effective transfer of maternal immunity. These findings illustrate that the recombinant L. paracasei oral vaccine can elicit robust mucosal, humoral, and cellular immune responses while providing maternal immune protection. Porcine epidemic diarrhea can be prevented and controlled with this strategy, which is both practical and promising.

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 Lactobacillus paracasei (L. paracasei) 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 L. paracasei 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 L. paracasei as a viable approach to the prevention and management of epidemic diarrhea in piglets.