Modular Nano-Antigen Display Platform for Pigs Induces Potent Immune Responses

Multivalent presentation of antigens using nanoparticles (NPs) as a platform is an effective strategy to enhance the immunogenicity of subunit vaccines and thus induce a high level of organismal immune response. Our previous results showed that pre-existing porcine circovirus type 2 (PCV2) antibodies could increase the antibody levels of nanoparticle vaccines carried in PCV2 VLPs. Here, we have established a generalized nanoantigen display platform, Cap-Cat virus-like particles (VLPs). By combining PCV2 VLPs with the modular linker element SpyTag003/SpyCatcher003 system, four porcine-derived viral protective antigens with different sizes and multimeric structures: the PRRSV B-cell epitope, the PEDV COE monomer, the CSFV E2 dimer, and the SIV HA trimer were efficiently demonstrated to elicit a strong immune response in mice. Crucially, the modification of antigens by the Cap-Cat VLPs platform enhanced the Th2 response and improved the Th1 response. The use of the platform demonstrates that HA antigen protects against lethal attacks by influenza viruses and reduces viral load in the lungs. We have demonstrated that the Cap-Cat VLPs platform demonstrates that antigens enhance the immune response by improving the processes of DC uptake, transport, lymph node (LN) localization, and immune cell activation. This "plug-and-display" assembly strategy facilitates the use of the Cap-Cat VLPs nanoantigen display platform for more applications and thus facilitates the development of more efficient, general-purpose porcine subunit vaccines.