In a respiratory infection model we study immune reactions in chickens infected with the low pathogenic avian influenza A H9N2 virus strain. For molecular immune response profiling we employed a recently developed chicken immuno-microarray containing approximately 5000 cDNA elements in duplicate (Smith et al., 2006 J. Smith, D. Speed, P.M. Hocking, R.T. Talbot, W.G. Degen, V.E. Schijns, E.J. Glass and D.W. Burt, Development of a chicken 5 K microarray targeted towards immune function, BMC Genomics 7 (2006), p. 49. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (0)Smith et al., 2006). In a first experiment, broiler-type chickens were either mock-immunized (referred to as non-immune), vaccinated with inactivated viral antigen only (immune), or with viral antigen in distinct Th1 or Th2 polarizing immunopotentiators (immune potentiated). Three weeks after vaccination all animals were given a respiratory infection with H9N2 via the oculo-nasal-intratracheal route. From these animals lungs and spleens were removed, RNA was isolated and subsequently used for microarray analysis. In general, we noted less host gene expression in immune potentiated, i.e. adjuvanted, birds when compared to non-immune, infected chickens. Immune potentiated birds showed reduced innate responses, mainly restricted to heat shock proteins, which, likely, are sufficient to control the pulmonary infection together with induced antibodies and T cells. Evaluation of the microarray data suggested gene pathways unique to or common amongst the differently immune groups (Degen et al., 2006). In subsequent experiments we have analyzed, and still are analyzing, the influence of age and type (broiler versus layer) of the chickens, challenge route (oculo-nasal-intratracheal versus spray), and the use of other immune response polarizing immunopotentiators on the host gene expression profiles by using the microarray and quantitative RT-PCR (Q-RT-PCR), as well as classical immune parameters. In this presentation we will highlight our findings. The data collected in this natural influenza A virus target Species, i.e. chicken, are of interest for the design of future human pandemic and seasonal vaccines containing immune response modifying immunopotentiators.