Porcine genetic markers of immunocompetence shape the immune response to a classical swine fever virus subunit vaccine

Breeding programs aimed at enhancing robustness and disease resistance in pigs represent a complementary strategy to biosecurity and vaccination measures. The objective of the present study was to validate a panel of genetic biomarkers and immunity phenotypes as indicators of the immune response to the E2-CD154 subunit vaccine against classical swine fever virus (CSFV). A total of 120 eight-week-old Duroc pigs were genotyped using a panel of six genetic markers, previously described as associated with innate and adaptive immunity traits. Additionally, total plasmatic IgG concentrations and SOX13 gene expression levels in blood were quantified. Based on these parameters, two genetically divergent groups (FAV and UNFAV) comprising 13 pigs each were selected and vaccinated twice on days 0 and 21 with the commercial vaccine. Serum samples were collected prior to vaccination and on days 14, 21, 28 and 35 post-vaccination. CSFV-specific antibody measures were assessed by ELISA targeting the E2 glycoprotein and by virus seroneutralization tests against three different CSFV strains. Vaccination with the E2-CD154 subunit vaccine induced strong humoral responses, with all animals developing high CSFV-E2–specific antibody levels by 14 days post-vaccination. The FAV group showed significantly higher ELISA and neutralizing antibody (NAb) titers than the UNFAV group, particularly at 21 days. After the second vaccine dose, all pigs reached high NAb titers, although group differences persisted for some CSFV strains. Animals in the FAV group exhibited higher frequencies of the A allele of SNP rs342772739 (associated with elevated γδ T cell counts and increased SOX13 expression), which, together with the G allele of SNP rs713631040 (associated with reduced serum C-reactive protein levels), showed the strongest association with NAb responses. Additional SNPs, rs80803525, rs319560097, rs338661853 and rs1113630513, also showed significant or suggestive associations with strain- and time-dependent variation in NAb responses. Our findings demonstrate the existence of genetic variability influencing the immune response to CSFV vaccination and identify a set of candidate genetic biomarkers associated with vaccine-induced humoral immunity in pigs.