Location: Endemic Poultry Viral Diseases Research
Project Number: 6040-32000-083-007-I
Project Type: Interagency Reimbursable Agreement
Start Date: Dec 1, 2020
End Date: Nov 30, 2025
Objective:
To date it is not known to what extent virus transmission (infectivity) is genetically controlled, nor how biosecurity measures such as vaccines impact it. This is because infectivity and virulence are often difficult to accurately measure, and up to now, appropriate experimental designs and statistical tools for estimating genetic infectivity especially with respect to virulence have been lacking. To overcome this knowledge gap, we focus on Marek’s disease virus (MDV), the most widely cited example of vaccine-driven viral evolution. The design of our experimental approach incorporates unique resources and highly controlled conditions to get large and accurate datasets, which will allow us to directly test the transmission-virulence trade-off theory and assemble empirical data with respect to the question whether indeed vaccination and/or host genetics drive viral transmission and virulence. Besides MDV, we also incorporate infectious bronchitis virus (IBV), an RNA coronavirus. The rationale is that MDV is genetically and antigenically stable, and virus replication is reportedly controlled mainly be the action of cytotoxic T cell (CTL) responses while IBV is known to be more variable genetically and antigenically, and immune evasion is thought to be mainly a consequence of escape from the action of neutralizing antibodies. In summary, the primary goal of this research is to collect accurate empirical data that will then feed into data-informed models of virus evolution and enhanced transmission as a function of vaccination status, host genetics, and viral mutation rates. We will also address the important and possibly interdependent questions of genome variability and evolution towards increased virulence in vivo. Specifically, we will test the hypothesis that the evolution of MDV and IBV towards increased virulence is a consequence of selective pressure on more proficient transmission and that such evolutionary processes are a function of (imperfect) vaccination, the host’s genetic makeup, and/or the mutation rate of the pathogen. Furthermore, the data garnered in these comprehensive animal experiments plus additional proposed surveys can be utilized to inform the generation of predictive models for disease development.
Specifically, we propose the following objectives to achieve scientific excellence and attain broader impact:
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. Develop an evolutionary-epidemiological simulation model
4. Disseminate information on Marek’s disease and the impact of vaccination to the broader public through K-12 training, workshops, online videos, seminars, and more.
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 infectious bronchitis virus (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 major histocompatibility complex (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 Marek's disease (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 Science, Technology, Engineering, and Mathematics (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.
