Simple SummaryHost genetics plays a significant role in the effectiveness of immune responses against pathogens. Disease severity for an individual or population is associated with dissimilarity in the levels of host gene expressions. In this study, the variations in the effects of host immune responsiveness between Taiwan Country and White Leghorn chicken breeds were investigated by next-generation sequencing. Overall, immune response-related genes between Taiwan Country chicken and White Leghorn chicken were expressed differently against live attenuated infectious bronchitis virus vaccination. The major histocompatibility complexes and cytokines were determined as significant players in determining the pattern and magnitude of immune responses following an infection. This study demonstrated the host genetic influences on the development of adaptive immune response between the Taiwan Country and the White Leghorn chickens after infectious bronchitis virus vaccination.AbstractThis study aims to identify the immune-related genes and the corresponding biological pathways following infectious bronchitis virus vaccination in Taiwan Country and White Leghorn chicken breeds. Transcriptomic analyses of the spleen of these two breeds were conducted by next-generation sequencing. Compared to White Leghorn chicken, Taiwan Country chicken showed a significantly higher level of anti-infectious bronchitis virus (IBV) antibodies at 14 and 21 days pos vaccination. At 7 days post vaccination, in the Taiwan Country chicken, higher expression of mitogen-activated protein kinase 10, Major histocompatibility complex class 1, and V-set pre-B cell surrogate light chain 3 were found. In contrast, the White Leghorn chicken had a high expression of interleukin 4 induced 1, interleukin 6, and interleukin 22 receptor subunit alpha 2. These findings have highlighted the variations in immune induction between chickens with distinct genetic background and provided biological pathways and specific genes involved in immune responses against live attenuated IBV vaccine.