Vaccination is crucial for health protection of poultry and therefore important to maintaining high production standards. Proper vaccination requires knowledge of the key players of the well-orchestrated immune system of birds, their interdependence and delicate regulation, and, subsequently, possible modes of stimulation through vaccine antigens and adjuvants. The knowledge about the innate and acquired immune systems of birds has increased significantly during the recent years but open questions remain and have to be elucidated further. Despite similarities between avian and mammalian species in their composition of immune cells and modes of activation, important differences exist, including differences in the innate, but also humoral and cell-mediated immunity with respect to, for example, signaling transduction pathways, antigen presentation, and cell repertoires. For a successful vaccination strategy in birds it always has to be considered that genotype and age of the birds at the time point of immunization as well as their microbiota composition may have an impact and may drive the immune reactions into different directions. Recent achievements in the understanding of the concept of trained immunity will contribute to the advancement of current vaccine types helping to improve protection beyond the specificity of an antigen-driven immune response. The fast developments in new omics technologies will provide insights into protective B- and T-cell epitopes involved in cross-protection, which subsequently will lead to the improvement of vaccine efficacy in poultry.

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