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The present study was performed to evaluate the findings in chickens vaccinated with various regimes and challenged with highly pathogenic avian influenza virus (H5). Forty SPF chicks were divided into four groups of 10 birds each, in which group I served as negative control. Group II was challenged with H5N1 avian influenza virus (positive control) at day 31. Group III was given inactivatedvaccine at day 10, then challenged with H5N1 virus at day 31. Group IV was vaccinated with recombinant fowlpoxvaccine at dayold and boosted with inactivated vaccine at day 10, then challenged with HPAIV at day 31. Quantitative RRT-PCR was carried out on tracheal swabs of living birds and organs of dead birds to evaluate viral load. In addition, specimens from trachea, lungs, bursa of Fabricius, spleen andbrain were collected from all birds for histopathologic, immunohistologic and electron microscopic examination. Viral RNA and antigen were demonstrated in examined organs in group II only using indirect immunoperoxidase and quantitative RRT-PCR. The pathological lesions detected were severe in group II, far less in group III and mild in groups I and IV. In conclusion, vaccination regime involving the use of two different vaccines resulted in much alleviation of the pathological alterations and conferred a better protection of chicken against highly pathogenic avian influenza than the use of one vaccine.