Engineered PCV2 VLPs for Antigen Delivery: A Platform for Next-Generation Veterinary Vaccines.

The capsid (Cap) protein of porcine circovirus type 2 (PCV2) self-assembles into virus-like particles (VLPs) that form stable, noninfectious nanoparticles with T = 1 icosahedral symmetry. Mimicking native virion architecture, these VLPs display antigens in a highly ordered array, conferring strong immunogenicity for both humoral and cellular responses. This review outlines the structural basis for their use as an antigen display platform, detailing molecular engineering strategies that target three defined sites, each with distinct functional roles: the N‑terminal for CD8+ T-cell activation, surface‑exposed loops for B-cell epitope presentation, and the C‑terminal for modular fusion of larger protein domains or targeting motifs. The impact of different expression systems on the production and immunogenicity of chimeric VLPs is further analyzed. Current challenges involve maintaining particle stability with high‑density antigen display and scaling up production. Ongoing advances in structure-guided design are paving the way for PCV2 VLPs to serve as a versatile platform for veterinary vaccines requiring balanced and potent immunity. Future efforts that integrate rational design with comprehensive evaluation in target species are expected to accelerate the development of effective multivalent vaccines.