Project Number: 6040-32000-082-000-D
Project Type: In-House Appropriated
Start Date: Oct 11, 2021
End Date: Oct 10, 2026
1. Identify the emergence of new vNDV strains. 1.A. Identify NDV genetic changes important for transmission and pathogenicity in poultry and wild birds. 1.B. Develop rapid identification assays for variant vNDV strains. 1.C. Conduct prevalence studies in poultry from countries where vNDV strains are endemic to determine the presence of variant and emerging viruses in NDV vaccinated poultry and the prevalence of NDV in wild birds. 2. Develop predictive models for risk assessment of virus evolution. 2.A. Develop predictive models using NextGen sequencing to evaluate the rate of change in different virulent NDV strains from unvaccinated, sub-optimally vaccinated, and well-vaccinated poultry. 2.B. Develop in vivo and ex vivo systems to understand the mechanisms of NDV evolution and adaptation. 3. Develop improved NDV vaccines platforms. 3.A. Determine and compare mucosal, cell, and early immune responses associated with protection elicited by available NDV vaccines to predict protection conferred by vaccination. 3.B. Identify and evaluate effective and user friendly NDV vaccine platforms for in ovo administration in broiler chickens. 3.C. Identify and evaluate low-cost vaccines that produce minimal vaccine reactions to prevent decreased productivity. 3.D. Develop NDV vaccine platforms capable of preventing viral replication, shedding, and transmission in domestic poultry.
We will conduct Newcastle disease virus (NDV) surveillance from poultry and wild birds in the United States and foreign countries to better understand the prevalence of NDVs and to identify important genetic markers that could change virus more fatal to poultry and also make it easier to transmit among birds. We will use state of the art Next Generation Sequencing (NGS) technology and bioinformatics tools to analyze large amounts of genetic information. Novel viruses that display evidence of increased virulence will be further characterized in animals. In conjunction with surveillance effort, we will vigilantly evaluate and update NDV diagnostic assays to assure that the official diagnostic assays used by National Animal Health Laboratory Network continue to perform with high sensitivity and specificity. In addition, we will develop new NGS-based diagnostic assays as a practical tool for the detection of previously known and newly emerging NDVs, and also for differentiation of low and highly virulent viruses. Like many other RNA viruses, NDVs continue to change and make them better fit to the environment. In this objective, we will study the complex interaction between virus and host. We will specifically assess: 1) how vaccine-induced immunity affect the evolution of NDV, 2) how NDV isolated from wild birds adapt in chickens, and 3) if specific gene or genetic marker determines how NDV replicates in birds or in specific tissues of the birds. The information obtained in this study will be used for risk assessment and applied to develop predictive model to improve control measures. We will study different aspect of immunity (innate, mucosal, antibody and cell mediated immunity) to predict protection conferred by vaccination and to develop new vaccines or further improve current vaccines. Interferons (IFN) are proteins made and released by host cells in response to viral infection and vaccination. In this objective, we will develop vaccines that modulate the IFN responses and enhance both innate and adaptive immune responses. The safety and protective efficacy of new vaccines will be evaluated in birds in comparison to currently available vaccines.