Preparation and Immune Protective Efficacy Evaluation of PCV2d Cap–COS Bioconjugate Candidate Vaccine

Porcine circovirus type 2 (PCV2) is one of the major pathogens currently threatening the global swine industry. The capsid protein (Cap) of PCV2 is a key antigen for developing subunit vaccines. In this study, we established a bioconjugation strategy using chitosan oligosaccharide (COS) to construct a covalently linked PCV2d Cap-COS complex via thiol-maleimide click chemistry. Immunization and challenge experiments in mice demonstrated that when formulated with JLC-3 adjuvant, the PCV2d Cap-COS complex induced stronger and more durable specific immune responses, significantly improved the average daily weight gain postchallenge, and effectively alleviated histopathological damage in the lungs and kidneys. These findings indicate that the PCV2d Cap-COS complex enhances both antigen structure and immunogenicity, offering a novel strategy and experimental evidence for developing high-efficacy PCV2d subunit vaccines.