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ARS Home » Southeast Area » Athens, Georgia » U.S. National Poultry Research Center » Endemic Poultry Viral Diseases Research » Research » Research Project #439583

Research Project: Influence of Vaccines, Host Genetics and Pathogen Mutation Rates on the Evolutionary Dynamics of Infectious Diseases - Purdue

Location: Endemic Poultry Viral Diseases Research

Project Number: 6040-32000-074-030-A
Project Type: Cooperative Agreement

Start Date: Jan 1, 2021
End Date: Nov 30, 2025

Objective:
To maintain human and animal health, it is extremely important to understand how pathogens like viruses are transmitted and evolve to higher virulence. This knowledge is especially important for sustainable disease control, particularly regarding the effectiveness of biosecurity, genetic selection, and vaccination. Thus, it is necessary to collect, assemble, and analyze highly informative as well as diverse but complementary datasets to determine the roles of these control measures on viral transmission and evolutionary dynamics. In this project, an international, interdisciplinary team investigates the impact of these approaches on the spread and evolution of two avian pathogenic viruses - Marek’s disease virus (MDV) and infectious bronchitis virus (IBV) – both of which are primarily controlled by imperfect vaccines. It has been argued that imperfect vaccines, such as those to MDV and IBV, or host genetic resistance may alter the balance of selection between pathogen transmission and virulence by allowing a few more divergent but still virulent strains to be transmitted at reduced cost. However, these hypotheses have not been proven, and predictive frameworks are lacking to determine the combined influence of host and viral genetics, as well as vaccination on viral transmission and evolution to increased virulence. To address these knowledge gaps, a series of transmission experiments have been designed utilizing unique resources and data from birds under highly controlled conditions. The goals of the proposed work are to collect high-resolution, empirical datasets to build the next generation of systems models incorporating host, viral, and management factors, as well as to establish the role of viral genome variability on virulence evolution. Furthermore, we will predict the combined influence of genetics, vaccination, and management practices on virus transmission, and assess the likely evolutionary dynamics in different socio-economic settings. This will be achieved through the following objectives: 1. Determine the influence of imperfect vaccines, host genetics, and viral mutation rate on transmission and evolution to higher virulence. 2. Validate viral genome polymorphisms associated with increased virulence and the ability of the virus to escape immune surveillance. 3. Build data-informed evolutionary-epidemiological simulation models to develop strategies to control the ecology, evolution and economic burden of MD. 4. Disseminate information on MDV and IBV, and the impact of vaccination to poultry producers and the public through training, workshops, online videos, seminars, and various engagement activities.

Approach:
Objective 1 - Our goal in Subobjective 1.1 is to examine downstream effect of vaccination on disease incidence in susceptible birds following 10 serial passages in live birds as well as to disentangle the influence of vaccine treatment on unvaccinated birds and vice versa. Subobjectives 1.2 and 1.3 will generate additional empirical datasets to determine the influence of host genetics and viral mutation rates, respectively. Subobjective 1.4 adds IBV, which enables us to compare and contrast two different avian pathogens, both controlled by imperfect vaccines, for viral transmission and virulence evolution. These large and accurate datasets will be analyzed to determine the influence of vaccination, host genetics, and viral mutation rate on transmission and evolution to higher virulence. Objective 2 - The initial inoculums used on Objective 1 and one isolate from each bird at passages 4, 7, and 10 will undergo whole genome sequencing. Computational analyses will detect variants and the key ones associated with increased virulence tested in recombinant viruses. Furthermore, variants that result in amino acid changes will be screened for their ability to escape presentation by specific MHC molecules to the immune system. Objective 3 - Predictive models. We will (1) develop a new generation of data-informed epidemiological-evolutionary models that allows us to assess the combined influence of host and viral genetics and vaccination on MD prevalence and risk for increased virulence evolution, and (2) combine the mathematical models with social science studies to identify effective and feasible solutions to mitigate disease spread and virulence evolution in domestic and commercial poultry populations in Sub-Saharan Africa. Objective 4 - training and outreach. Various modules are developed for education, e.g., (1) Engage 4-H youth and leaders in interactive STEM-based online modules and hands-on component to increase their understanding of biosecurity measures and vaccines as they relate to the U.S. poultry industry and (2) Promote interest and agricultural literacy and education in elementary school 4th and 5th grade students with the development of a one-day workshop designed to integrate STEM with poultry and basic immunology concepts. Outreach efforts include (1) Develop extension bulletins for poultry breeders, (2) Develop training modules for small flock and commercial industry, (3) Design an interactive exhibit for use at fairs and events to relay concepts and prevention ideas, (4) Host webinar through extension for small flock, (5) Get speaking engagements with Midwest Poultry Federation to disseminate findings, and (6) Submit proposed symposium to Poultry Science.