YY-EEID US-UK Collab: Combined influence of imperfect vaccines, host genetics, and non-genetic drivers on virus transmission and virulence evolution

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Summary (up to 4000 characters)To maintain human and animal health, it is extremely important to understand how pathogens like viruses are transmitted and evolve to higher virulence. It is this knowledge that enables employment of effective and sustainable control strategies. Thus, it is necessary to collect, assemble, and analyse highly accurate datasets to determine the short- and long-term effectiveness of disease control approaches, that include biosecurity, genetic selection for disease resistance, and widespread vaccination. 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 like 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 for determining 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 that utilize unique resources and data from 7,000+ birds under highly controlled conditions. In summary, the primary goal of this research is to collect informative, high-resolution empirical data and use these to build the next generation of data-informed mathematical models of virus transmission and evolutionary dynamics as a function of vaccination status, host genetics, and/or viral mutation rates. We will also address the important and possibly interdependent questions of genome variability and evolution towards increased virulence in vivo.Besides the pure scientific merit of this research, we also strive towards lifting the project to high practical relevance. This requires a whole systems approach that also considers the broader socio-economic and political drivers of disease spread and virulence evolution. We will combine socio-economic studies with mathematical modelling to identify strategies for mitigating MD spread and MDV virulence evolution in sub-Saharan Africa, where poultry production is currently undergoing drastic increases in commercial production, similar to what was observed in the US in the 1960s.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. 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