Newcastle is viral avian disease effecting a wide range of wild and domestic bird species. It is highly contagious and present a major problem to the poultry industry as it causes severe respiratory and nervous symptoms. Newcastle disease in poultry is controlled by using a live lentogenic (attenuated) virus as a vaccination strategy. However, due multiple field strains and the rapid change of the virus, vaccination efficiency is decreasing rapidly. To improve vaccination efficiency and to overcome some of the limitations associated with live virus vaccination, we have developed a novel vaccination based on protein subunits derived from virulent Newcastle strains. To identify protecting protein subunits we use the genome sequence of a large array of field strains to conduct a sequence and structural analysis from which unique protein sequences are extracted. The novel protein subunits are expressed in a microbial system designed to produce large quantities of proteins with native like structure and properties. This combined strategy leads to high antibodies titers in chickens and may provide an efficient strategy to live virus vaccine.