Global dynamics of vaccine effectiveness and genotype shift in porcine circovirus 2: A cross-temporal analysis

Porcine circovirus type 2 (PCV2) has caused annual economic losses exceeding US$2 billion to the global swine industry, with mortality rates of 5%-20% in unvaccinated herds. Following the 2006 introduction of PCV2a-based vaccines in 2006, genotype dominance shifted sequentially from PCV2a to PCV2b and from 2010 onward to PCV2d. However, a unified, long-term evaluation of how vaccine uptake influences genotype prevalence and viral evolution remains unavailable.

This study aims to quantify the spatio-temporal relationship between vaccine coverage and genotype shifts, compare genotype-specific vaccine-efficacy decay, and identify capsid-protein sites under positive selection in the post-vaccine era.

Annual genotype frequencies (2000-2025) were extracted from OIE surveillance reports, PCV2 cap-gene sequences were retrieved from GenBank, and vaccine-efficacy figures were compiled from peer-reviewed studies. A reproducible pipeline was used to harmonize these streams into three datasets: genotype prevalence, country-level coverage, and time-indexed efficacy. LOESS smoothing and linear mixed-effects models assessed coverage-prevalence associations. The exponential decay parameters (VE-, k) were estimated via random-effects meta-regression. Codon-level selection was evaluated using MEME on post-vaccination alignments.

Vaccine coverage was inversely correlated with PCV2a prevalence (ρ = -0.72, p < 0.001) and positively with PCV2d (ρ = 0.23, p < 0.001). The initial efficacy (VE-) was higher and the decay was slower for PCV2a (95.2%; k = 0.038 month^-¹) than for PCV2d (79.4%; k = 0.092 month^-¹). Twelve capsid codons exhibited significant positive selection after vaccine rollout, with several overlapping known neutralizing epitopes.

PCV2 vaccination exerts selective pressure driving genotype succession. The accelerated waning of protection against emergent genotypes and the emergence of escape-associated mutations at key antigenic sites support the development of multivalent vaccines incorporating PCV2d antigens to sustain long-term herd immunity.