Studies leading to sustainable strategies for the control of Marek's disease: Is vaccination responsible for virulence evolution in Marek's disease?

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We propose a combination of single-generation and multi- generation experiments to test the hypothesis that the prolonged and widespread use of imperfect (leaky) vaccines has been responsible for the increasing virulence of Marek's disease virus over the last half century. Viral strains inducing the symptoms originally described by Marek can no longer be isolated in intensified commercial poultry operations in the US and Europe, having been replaced with hyperpathogenic strains which induce very rapid morbidity and mortality. The fundamental data required to determine whether vaccination is responsible for this evolution are the aim of this proposal. We will (a) determine the most appropriate measures of evolutionary fitness for MDV, using a combination of transmission experiments and quantitative PCR of feather dust, feathers, skin and blood, (b) compare the fitness of strains varying in virulence in vaccinated and unvaccinated birds, and (c) experimentally evolve an MDV strain through vaccinated and unvaccinated birds. The data we obtain from these experiments would also enable the testing a number of explanations for virulence evolution. If the vaccine hypothesis is correct, we will find that vaccination reverses the relative fitness of mild and virulent strains of MDV, and that virulence evolves upwards more rapidly in vaccinated birds. This will directly contribute to MDV management, but more broadly, will determine whether there are other diseases - agricultural and human - where widespread use of leaky vaccines could lead to the evolution of pathogen strains which put the unvaccinated at greater risk.

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