Oral Immunization against PEDV with Recombinant Lactobacillus casei Expressing Dendritic Cell-Targeting Peptide Fusing COE Protein of PEDV in Piglets

Abstract

Porcine epidemic diarrhea (PED) is a highly contagious disease in newborn piglets. In our previous study, a genetically engineered Lactobacillus casei oral vaccine (pPG-COE-DCpep/L393) expressing a dendritic cell (DC)-targeting peptide fused with porcine epidemic diarrhea virus (PEDV) COE antigen was developed. This vaccine induced significant levels of anti-PEDV specific IgG and IgA antibody responses in mice, indicating a potential strategy against PEDV infection. In this study, pPG-COE-DCpep/L393 was used for oral vaccination of newborn piglets against PEDV. We then assessed the immune responses and protection efficacy of pPG-COE-DCpep/L393. An indirect enzyme-linked immunosorbent assay (ELISA) showed that the recombinant Lactobacillus vaccine elicits a specific systemic and mucosal immune response. The T-helper cells mediated by pPG-COE-DCpep/L393 and PEDV infection display a Th1 phenotype. The histopathological results showed that pPG-COE-DCpep/L393 promotes lymphocyte proliferation and effectively protects piglets against PEDV infection. The transforming growth factor-β level indicated that the recombinant Lactobacillus vaccine plays a role in anti-inflammatory responses in mesenteric lymph nodes during PEDV infection. These results show that pPG-COE-DCpep/L393 is a potential vaccine against PEDV infection.

Host Factors Affecting Generation of Immunity Against Porcine Epidemic Diarrhea Virus in Pregnant and Lactating Swine and Passive Protection of Neonates

“…Recently, Wang and colleagues generated a recombinant Lacotobacillus (L393) to secrete a DC-targeted peptide conjugated to PEDV antigen. After oral vaccination in neonatal piglets, this probiotic vaccine (pPG-COE-DCpep/L393) elicited PEDV-specific IgA and IgG antibodies and IFN-γ-producing CD4 + T cells [70]. These results are similar to those described earlier where sows vaccinated with a DC-targeted PEDV vaccine had increased IFN-γ-producing CD4 + T cells (Th1 phenotype).…”

“…For example, in piglets, monocyte-derived DCs (mo-DCs) expand upon PEDV infection in vivo [67] and alter cytokine responses in vitro [67,68]. DC-targeting approaches for PEDV vaccines generated neutralizing antibody responses and provided partial protection against PEDV infection [69,70]. However, there is contrasting evidence regarding the ability of PEDV to productively infect DCs [67,71].…”

Identification of the immunodominant neutralizing regions in the spike glycoprotein of porcine deltacoronavirus

“…Vaccine development has therefore been focused exclusively on the COE epitope. An oral vaccine (pPG-COE-DCpep/L393), a recombinant Lactobacillus casei that expresses DC-targeting peptide fused with a COE protein, was developed by Hou et al (Hou et al, 2018).…”

Oral delivery of maize-produced porcine epidemic diarrhea virus spike protein elicits neutralizing antibodies in pigs

“…Precedent for oral immunization for PEDV includes a number of studies expressing PEDV S or N proteins in probiotics such as Lactobacillus. Feeding of these products elicits an immune response and protection upon challenge in a mouse model (Di-qiu et al 2012;Hou et al 2018). The PEDV spike protein has also been produced in tobacco (8-20 µg/g wet weight or up to 5% total soluble protein (TSP)), rice (0.083% TSP), and other plants, and elicits an immune response with neutralizing activity against the virus in mice (Bae et al 2003) (Kang et al 2005) (Huy et al 2012;Huy and Kim 2019).…”