Project Number: 6040-32000-064-00-D
Project Type: Appropriated
Start Date: Oct 11, 2011
End Date: Oct 10, 2016
1. Determine the impact of variant and emerging viruses on the development and control of Newcastle disease by developing means to detect and survey variant and emerging Newcastle disease viruses and by determining the presence of variant and emerging Newcastle disease viruses in wild birds and live poultry markets. 1.A. Determine the impact of variant and emerging viruses on the evolution and control of Newcastle disease by determining the presence of variant and emerging Newcastle disease viruses in wild birds and live poultry markets. 1.B. Develop means to detect and survey variant and emerging Newcastle disease viruses. 2. Elucidate the host-pathogen interactions of Newcastle disease virus infections that impact vaccine efficacy by defining host pathways modulated by Newcastle disease viral infections and by identifying genetic and biological viral determinants that affect the safety and efficacy of Newcastle disease vaccine virus strains. 2.A. Define host response pathways modulated by Newcastle disease viral infections. 2.B. Identify viral determinants that affect the safety and efficacy of Newcastle disease vaccine virus strains. 3. Develop vaccine strategies to effectively control Newcastle disease and stop disease outbreaks by developing vaccine platforms specifically designed to control low virulent and virulent Newcastle disease outbreaks. 4. Develop a predictive biology approach to understand disease pathogenesis for Newcastle disease virus. 4.A. Use bioinformatics analysis to generate hypothesis on pathogenesis, host range, and virulence factors for Newcastle disease virus and to improve molecular diagnostics. 4.B. Use a reverse genetics approach to test hypothesis on pathogenesis, host range, and virulence factors for Newcastle disease virus.
Field samples of Newcastle disease virus (NDV) collected from poultry, cormorants, pigeons, wild birds, and live bird markets from the U.S. and abroad will be characterized by genomic nucleotide sequencing and by performing virulence testing. Sequence variants or genetically diverse isolates will be biologically evaluated by determining the mean death time in eggs (MDT) and the intra-cerebral pathogenicity index (ICPI) in one day old chicks. Viruses of novel lineages that display evidence of increased virulence will be further characterized in specific pathogen free chickens by conducting standard pathogenesis experiments. Field samples from exotic viruses and viruses circulating in U.S. wild bids, and live bird market will be evaluated using available real time rapid detection assays (fusion, matrix and polymerases gene based) and those samples that fail detection with any of the U.S. Department of Agriculture (USDA) real time polymerase chain reaction rapid tests will be further analyzed using classical virological techniques or random sequencing. We will construct chimeric vaccine viruses by replacing the surface fusion and hemagglutinin-neuraminidase proteins from current circulating virulent field strains onto a tested vaccine backbone (LaSota). The effect of replacing these genes on virulence, clinical signs, tissue tropism, viral shedding, and induction of antigenic and protective response will be evaluated in animals experiments using immunologically mature chickens. Vaccination-challenge experiments will be performed to evaluate how well new circulating Asian, African and South American virulent viruses perform during current commercial vaccination schemes. Current vaccines such as LaSota or B1 will be used to vaccinate birds and clinical signs, pathological outcomes, viral replication and shedding will be compared after challenges with emerging strains of NDV. Live vaccines viruses expressing genes of NDV from viruses of recent outbreaks will be evaluated with the expectation that improved protection will result. This increased protection after virulent challenge should effectively reduce transmission from vaccinated animals and provide better clinical protection. Additionally, utilizing recombinant technology live vaccines expressing chicken cytokines will be developed.