Combating highly pathogenic avian influenza: Novel vaccination strategies using recombinant live avian viral vaccine vectors. THIS GRANT IS A SUPPLEM

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We propose to use novel approaches for AI vaccination using recombinant herpesvirus of turkey (HVT) and avian infectious bronchitis virus (IBV) as vaccine vectors that express protective haemagglutinin (HA) and neuraminidase (NA) antigens of avian influenza virus. Since these vaccine constructs will express only selected AI antigen, vaccinated birds can be unambiguously differentiated from those infected with the field virus. These virus vectors have several distinct advantages: (1) they are extensively used as live virus vaccines. (2) they induce immunity following in ovo vaccine application. (3) it is relatively easy to generate new vaccines from the specific field isolates. Recombinant HVT and IBV vectors will be generated by cloning HA and NA genes (the multiple basic amino acids at the HA1 and HA2 cleavage sites will be deleted) from the HPAI viruses, [A/os/Italy 984/00 (H7N1) and A/ty/Turkey/1/05 (H5N1)], into the HVT and IBV genomes using in house derived reverse genetics systems. We plan to generate a panel of recombinant viruses (1) HVT/H7/N1 (2) HVT/H5/N1 (3) IBV/H7 (4) IBV/H5 (5) IBV/N1 for use as potential vaccine candidates. The recombinant viruses will be evaluated for expression of the AI-derived HA and NA genes in cell culture and in ovo. Selected viruses will be used in homologous virus challenge studies in chickens for comparison with commercially available inactivated vaccines. The protection parameters of the vaccines candidates will be assessed by comparing the immune responses, mortality rates, morbidity and shedding of AI virus from the challenged birds. The data obtained from these experiments will enable us to select the most effective vaccine candidate providing protection against challenge with HPAI AI virus and decrease in excretion of the AI virus. Ultimately, we anticipate that these novel AI vaccines will be used in the eradication of AI by the control of disease and reduction of viral load in the environment.