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.