A Novel Inactivated Vaccine Based on an Emerging PEDV GIIc Variant Provides Cross-Protection Against Heterologous GII Strains

Background/Objectives: Porcine epidemic diarrhea virus (PEDV), particularly the emerging GII genotype, poses a severe threat to the swine industry in affected regions, primarily in Asia. Current vaccines based on classical strains often provide limited cross-protection against these heterogeneous variants, though it should be noted that these vaccines are primarily designed to induce maternal immunity in sows. The objective of this study was to develop a novel inactivated vaccine using an emerging PEDV GIIc variant and evaluate its immunogenicity and cross-protective efficacy against heterologous strains. Methods: A novel PEDV strain, designated PEDV-HeN2024, was isolated from clinical samples and identified through cell culture, immunofluorescence assay (IFA), genetic sequencing, and phylogenetic analysis. An inactivated vaccine was prepared by emulsifying the purified virus with ISA 201 VG adjuvant (1:1, v/v). Immunogenicity was assessed in piglets by measuring virus-neutralizing antibody titers and PEDV-specific IgG levels. Cross-protective efficacy was evaluated through in vitro neutralization assays and in vivo challenge studies with homologous GIIc and heterologous GIIa and GIIb strains. Results: The isolated PEDV-HeN2024 strain demonstrated pathogenicity, causing severe diarrhea and 100% mortality in PEDV-naïve neonatal piglets. Sera from vaccinated animals showed potent cross-neutralizing activity against homologous GIIc, as well as heterologous GIIa and GIIb strains. In challenge studies, vaccinated piglets were significantly protected against clinical disease, showing no diarrhea or viral shedding, and maintained normal intestinal architecture. Conclusions: The inactivated vaccine developed from the emerging PEDV GIIc variant elicits robust humoral immunity and provides cross-protection against prevalent heterologous GII strains. These findings highlight its potential as a promising spectrum vaccine candidate for controlling PEDV outbreaks. This study underscores the importance of using recently circulating strains for vaccine development to overcome the limitations of current vaccines.