Host genetics and pre-vaccination blood transcriptome as determinants of vaccine-induced immunity to Influenza A virus in swine

Influenza A virus (IAV) is a major respiratory pathogen in pigs, causing diseases that have significant economic and potential public health consequences. Vaccine effectiveness varies among animals, impacting long-term herd protection due to individual variabilities in antibody levels and persistence over time. Our aim was to identify the genetic factors and pre-vaccination blood transcriptomic profiles that influence immune response levels to the IAV vaccine. A total of 187 piglets were vaccinated at weaning (28 days of age, 0 days post-vaccination, dpv) and boosted three weeks later, and humoral responses were assessed until slaughter (21, 28, 35, and 118 dpv) by measuring serum IAV-specific IgG and hemagglutination inhibition (HAI) titers. The results revealed varying antibody responses and persistence. Genome-wide association studies identified two loci on chromosomes SSC5 and SSC8 associated with a persistence of HAI titers until slaughter. Pre-vaccination blood transcriptomic analyses showed that early and post-boost antibody responses (21, 28 and 35 dpv) and long-term persistence (118 dpv) were associated with distinct baseline immune programs, with extracellular matrix and myeloid-related signatures predicting strong early and peak responses, whereas interferon-related signatures were linked to reduced long-term antibody persistence. Our results highlight the importance of considering the role of immune competence and genetics in vaccine responses in pigs and suggest candidate biomarkers to improve vaccination strategies within breeding programs.