Genetic influence underlying individual variation in vaccine responses in a White Leghorn laying hen line

Vaccination is an essential part of poultry health, yet considerable variability in vaccine efficacy among individuals poses challenges for disease control and productivity. The genetic basis underlying this variability remains poorly understood. This study aimed at providing new insights into the genetic architecture underlying vaccine responses in poultry by identifying the genetic loci controlling the immune response to several vaccines. To reach this purpose, we studied 537 White Leghorn hens, focusing on vaccines against Newcastle Disease Virus (NDV), Infectious Bronchitis Virus (IBV), Avian Encephalomyelitis Virus (AEV), and Avian Pneumovirus (APV). Humoral immune responses were assessed for all vaccinations at multiple post-vaccination time points, and cellular immune responses were evaluated for the NDV vaccine at the end of the experiment. Important individual variabilities in vaccine responses were observed within this population, with some animals failing to mount antibody responses to the vaccinations. Heritability estimates among responder animals for antibody levels treated as a continuous trait (51 to 472 animals) indicated low to moderate genetic influence (0.00-0.39), whereas analysing vaccine response as a binary trait (392 to 537 animals) distinguishing responders from non-responders revealed a moderate to high genetic contribution (0.22-0.40). Furthermore, genetic and phenotypic correlation analyses revealed complex relationships among vaccine response traits, including weak positive and even negative genetic correlations, both across different vaccines and within the same vaccination at different time points. Genome-wide association studies (GWAS) identified significant quantitative trait loci (QTL) on chromosomes 1, 4, 5, 8, 11, 15, and 28, associated with immune traits. QTLs were detected for both levels of the response and responders vs non-responder’s traits. Functional annotation of these loci highlighted several genes of interest, including MKNK1, TRABD2B, BRCA2, ROBO1, HMGB1, MAPK3, CLEC3A, MAF, ZAP-70, and RFX2, as well as the non-coding RNA vaultRNA, all of which may contribute to immune response variability. In addition, Gene Set Enrichment Analysis identified immune-related pathways, particularly those involved in T-cell responses and plasmacytoid dendritic cell activation, further supporting the role of genetic regulation in vaccine-induced immunity. These findings demonstrate that a complex genetic regulation significantly contributes to vaccine response variability in White Leghorn hens. By pinpointing candidate genes and pathways, this study shows that incorporating immune traits into selective breeding programs may ultimately contribute to improved vaccine efficacy in production systems.