Knowledge gaps in research and control of porcine circovirus 2 (PCV2) infections.

Porcine circovirus type 2 (PCV2) remains one of the most important pathogens in swine production, associated with a spectrum of clinical conditions collectively termed PCV2-associated diseases. Despite the remarkable success of vaccination programs, which have drastically reduced the incidence of systemic disease and reproductive disorders, PCV2 continues to circulate globally in both domestic and wild swine populations. Its high evolutionary rate, capacity for recombination, and broad host plasticity raise ongoing concerns regarding viral persistence and long-term control. This review synthesizes current knowledge and identifies critical research gaps that hinder the development of sustainable PCV2 control strategies. While vaccines effectively mitigate clinical disease, they do not fully prevent infection or virus shedding, thereby allowing continued circulation and genetic diversification. The biological consequences of this viral evolution—including potential impacts on cross-protection, virulence, and vaccine escape—remain insufficiently understood. Similarly, the role of host immunity, co-infections, and environmental or management factors in modulating disease outcomes is incompletely characterized. A deeper understanding of the mechanisms underlying PCV2 pathogenesis, including immune modulation and determinants of subclinical versus clinical outcomes, is urgently needed. Diagnostic approaches have also evolved, with molecular techniques such as quantitative PCR largely replacing histopathology and immunohistochemistry. While highly sensitive, these methods cannot establish causal relationships between viral presence and disease, underscoring the need for integrated diagnostic frameworks. In addition, harmonized thresholds for viral load quantification and standardized serological assays to assess protective immunity are lacking, limiting comparability across studies and surveillance systems. Future priorities should include the development of next-generation vaccines capable of inducing sterilizing immunity, investigation of optimal vaccination schedules in the context of maternally derived antibodies, and exploration of innovative vaccine delivery platforms. Furthermore, integrated surveillance strategies combining molecular epidemiology, wildlife monitoring, and international data sharing will be essential to track viral evolution and detect potential vaccine breakthroughs. Addressing these knowledge gaps will require coordinated efforts across fundamental, applied, and translational research, aligned with the needs of veterinarians and the swine industry. Only through such an integrated agenda can the sector advance from disease control towards the long-term goal of PCV2 elimination.