The C3d-fused Porcine circovirus type 2d virus-like particle induced early and enhanced immune response and protected pigs against challenge.

Porcine circovirus type 2 (PCV2) is an economically significant pathogen affecting the global swine industry. Vaccination is considered the most effective and best way to prevent PCV2-associated disease. The PCV2d genotype has become predominant by replacing the previous PCV2b genotype. The potential increase in the virulence of PCV2d has drawn attention, spurring the development of PCV2d vaccines. Virus-like particle (VLP) is an ideal vaccine candidate for its safety and potent immunogenicity. C3d is a molecular adjuvant that can be used to promote the protective efficacy of the PCV2 vaccine. In this study, we expressed PCV2d Cap protein fused with C3d epitope using E. coli expression system. The purified recombinant Cap protein assembled into VLP, which was designated as PCV2d-C3d-VLP. Through assessments in mice and piglets, we demonstrated that the PCV2d-C3d-VLP elicited robust humoral responses, notably accelerating antibody production one week earlier compared to a commercial PCV2d subunit vaccine. Furthermore, vaccination substantially reduced PCV2d viral load in piglets. These results present an innovative strategy for developing a more efficacious and cost-effective PCV2d VLP vaccine.