Abstract

Porcine circovirus-associated disease (PCVAD), caused by pathogenic porcine circovirus type 2 (PCV2), remains one of the most economically devastating diseases in the global swine industry, and the continued emergence and predominance of the PCV2d genotype have raised concerns regarding the efficacy of currently available vaccine. In this study, a virus-like particle (VLP) subunit vaccine based on the PCV2d capsid protein was developed using a prokaryotic expression system, and its immunogenicity and protective efficacy were systematically evaluated in pigs. Following immunization and subsequent homologous PCV2d challenge, vaccinated pigs exhibited significantly attenuated clinical manifestations, including reduced rectal temperature elevation and less impairment of average daily weight gain during the early phase of infection. Moreover, vaccination resulted in markedly decreased viral DNA loads in serum and multiple tissues, including the lungs, spleen, kidneys, and inguinal and mesenteric lymph nodes, compared with unvaccinated challenged controls. The VLP vaccine also induced robust humoral immune responses, characterized by elevated PCV2-specific IgG and neutralizing antibody titers, and effectively mitigated PCV2d-associated histopathological lesions in the lungs and lymph nodes. Importantly, immunized pigs showed alleviation of peripheral T-lymphocyte depletion, with higher levels of CD3+, CD4+, and CD8+ T cells following challenge. Collectively, these findings demonstrate that the PCV2d capsid-based VLP subunit vaccine confers effective protection against PCV2d infection and represents a promising candidate for the prevention and control of PCVAD.