Development and immunogenicity of adenoviral Fc-fused FMDV virus-like particle vaccine in swine.

Foot-and-mouth disease (FMD) remains a major threat to global livestock health, and current inactivated vaccines face limitations in biosafety and cross-protection. Virus-like particle (VLP) -based vaccines offer a safer alternative, however, their production is often hindered by the cytotoxicity of the viral 3C protease. In this study, we developed a modified 3C protease with reduced cytotoxicity, enabling efficient expression of FMDV VLPs via an internal ribosome entry site (IRES)-based system. To enhance immunogenicity, the swine IgG Fc fragment (sFc) was genetically fused to the VLP capsid protein by modifying the VP1-2A region, resulting in successful surface display of sFc on the VLPs. The modified VLPs were then incorporated into a replication-defective adenoviral vector (Ad5), allowing for efficient antigen delivery and presentation. Immunization of swine with the Ad5-FMDV VLP-sFc vaccine elicited robust FMDV-specific IgG and neutralizing antibody responses, along with a balanced Th1/Th2 cytokine profile. These findings suggest that the Ad5-FMDV VLP-sFc construct is a promising FMD vaccine candidate with enhanced safety and immunogenic potential.