Parenterally Administered Porcine Epidemic Diarrhea Virus-Like Particle-Based Vaccine Formulated with CCL25/28 Chemokines Induces Systemic and Mucosal Immune Protectivity in Pigs

Abstract

Generation of a safe, economical, and effective vaccine capable of inducing mucosal immunity is critical for the development of vaccines against enteric viral diseases. In the current study, virus-like particles (VLPs) containing the spike (S), membrane (M), and envelope (E) structural proteins of porcine epidemic diarrhea virus (PEDV) expressed by the novel polycistronic baculovirus expression vector were generated. The immunogenicity and protective efficacy of the PEDV VLPs formulated with or without mucosal adjuvants of CCL25 and CCL28 (CCL25/28) were evaluated in post-weaning pigs. While pigs intramuscularly immunized with VLPs alone were capable of eliciting systemic anti-PEDV S-specific IgG and cellular immunity, co-administration of PEDV VLPs with CCL25/28 could further modulate the immune responses by enhancing systemic anti-PEDV S-specific IgG, mucosal IgA, and cellular immunity. Upon challenge with PEDV, both VLP-immunized groups showed milder clinical signs with reduced fecal viral shedding as compared to the control group. Furthermore, pigs immunized with VLPs adjuvanted with CCL25/28 showed superior immune protection against PEDV. Our results suggest that VLPs formulated with CCL25/28 may serve as a potential PEDV vaccine candidate and the same strategy may serve as a platform for the development of other enteric viral vaccines.

Transcriptomics yields valuable information regarding the response mechanisms of Chinese Min pigs infected with PEDV

“…Furthermore, we performed transcriptome analysis of jejunum tissues and identified the key PCGs, lncRNAs, and miRNAs involved in the immune responses of Min pigs infected with PEDV, which provided important information on virus-host interactions for deciphering the mechanism of virus infection. PEDV infection resulted in apoptosis and necrosis of small intestinal absorptive epithelial cells and a decrease in the ratio of villous height to crypt depth (26,27). In this study, all the infected piglets showed significant intestinal lesions, and the death individuals were more serious than the resistant individuals.…”

“…CXCL9 secreted by PEDV-infected IPEC-J2 cells significantly regulated the number of T-cell subpopulations in the peripheral blood cells of piglets, and high expression of CXCL13 significantly increased the number of B-cell migrations ( 34 ). The synergistic role of CCL25 and CCL28 in translocating IgA cells into the intestine had been demonstrated in mice, and pigs immunized with CCL25/CCL28 adjuvant virus-like particles showed excellent immune protection against PEDV ( 26 , 35 ). In this study, CXCL8, CXCL2, CXCR6, CXCL9, CXCR4, CXCL8, CXCR6, CXCR4, CX3CL1, CCL19, CCL4, CCL21, CCL26, CCL28, and CCL11 showed higher expressions in the infected group than that in the control group, while CX3CR1, CXCL14, CCL5, and CCL16 had lower expressions in the infected group than that in the control group.…”

“…PEDV infection resulted in apoptosis and necrosis of small intestinal absorptive epithelial cells and a decrease in the ratio of villous height to crypt depth ( 26 , 27 ). In this study, all the infected piglets showed significant intestinal lesions, and the death individuals were more serious than the resistant individuals.…”

Porcine Epidemic Diarrhea: Insights and Progress on Vaccines

“…These antibodies conferred protection against PEDV infection in Vero cells. Using a multicistronic baculovirus expression system, Hsu and colleagues successfully created VLPs incorporating the S, M, and E structural proteins of PEDV [ 123 ]. Their research revealed that pigs immunized intramuscularly developed a systemic immune response characterized by anti-PEDV S-specific IgG and cellular immunity.…”

Combination of S1–N–Terminal and S1–C–Terminal Domain Antigens Targeting Double Receptor-Binding Domains Bolsters Protective Immunity of a Nanoparticle Vaccine against Porcine Epidemic Diarrhea Virus

“…Antibodies targeting the receptor-binding domain (RBD) of the S1 protein can neutralize coronavirus infection by blocking virus binding to cell receptors . Considerable effort has been devoted to the development of PEDV vaccines that target the S1 protein. − However, there is still a lack of effective vaccines against variant strains of PEDV, due to its low immunogenicity and the difficulty with rapidly replacing antigens. Ferritin (Fer) is essential for the proper storage of iron in the body.…”