Why are pathogens not more virulent? Conventional wisdom (and one of the key mathematical models in the ecological and evolutionary theory of infectious diseases) is that evolution removes excessively lethal Strains. Pathogens that kill their hosts too rapidly shorten their own infectious periods and hence have lower evolutionary fitness than less lethal strains. If so, what happens when vaccines protect hosts from death? Gould immunization enable the circulation of strains that would once have been removed by natural selection? That would increase the net virulence of pathogen population experienced by unvaccinated hosts. The 'evolutionary risk' of public and animal health measures cannot be directly assessed in clinical trials because pathogen evolution will be seen only after population-wide implementation. We have recently shown experimentally that vaccination does indeed make possible the onward transmission of hyperpathogenic strains of Marek's disease virus (MDV) in poultry. We seek to now to dissect the effects of immunization on the ecology of transmission in this farm animal system, so as to evaluate the impact of contemporary and next generation vaccines on the future evolution of this disease. We will fuse experimental measurements of virus transmission from vaccinated and unvaccinated birds, field investigations of farm epidemiology and mathematical evolutionary-epidemiological models. Our primary objective is to dissect the selective forces imposed by immunization and other management pratices on MDV virulence, and to evaluate their evolutionary and epidemiological consequences. This will make it possible to use evolutionary epidemiological models to analyze evolutionary trajectories and to assess the evolutionary consequences of contrasting management strategies on the evolution of MDV and other pathogens. The biology and ecological context of MDV offer unprecedented scientific opportunities.
We aim to make MDV a canonical case study of pathogen adaptation and disease emergence in response to human-induced environmental change.

Public Health Relevance

Our work will make it possible to evaluate the risk that some types of vaccines allow pathogens to circulate which are so virulent that they would normally be removed by natural selection. The emergence of high-path farm animal diseases can have implications for animal and human health (e.g. avian influenza) - and it is also possible next generation human vaccines might drive the evolution of more virulent pathogens.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IDM-U (55))
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Eckstrand, Irene A
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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Kennedy, David A; Read, Andrew F (2018) Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance. Proc Natl Acad Sci U S A 115:12878-12886
Kennedy, David A; Dunn, Patricia A; Read, Andrew F (2018) Modeling Marek's disease virus transmission: A framework for evaluating the impact of farming practices and evolution. Epidemics 23:85-95
Kennedy, David A; Cairns, Christopher; Jones, Matthew J et al. (2017) Industry-Wide Surveillance of Marek's Disease Virus on Commercial Poultry Farms. Avian Dis 61:153-164
Kennedy, David A; Read, Andrew F (2017) Why does drug resistance readily evolve but vaccine resistance does not? Proc Biol Sci 284:
Pandey, Utsav; Bell, Andrew S; Renner, Daniel W et al. (2016) DNA from Dust: Comparative Genomics of Large DNA Viruses in Field Surveillance Samples. mSphere 1:
Kennedy, David A; Kurath, Gael; Brito, Ilana L et al. (2016) Potential drivers of virulence evolution in aquaculture. Evol Appl 9:344-54
Day, Troy (2016) Interpreting phenotypic antibiotic tolerance and persister cells as evolution via epigenetic inheritance. Mol Ecol 25:1869-82
Read, Andrew F; Baigent, Susan J; Powers, Claire et al. (2015) Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens. PLoS Biol 13:e1002198
Kennedy, David A; Dunn, John R; Dunn, Patricia A et al. (2015) An observational study of the temporal and spatial patterns of Marek's-disease-associated leukosis condemnation of young chickens in the United States of America. Prev Vet Med 120:328-35