Studies leading to sustainable strategies for the control of Marek's disease: Is vaccination responsible for virulence evolution in Marek's disease?
Lead Research Organisation:
The Pirbright Institute
Department Name: Div of Microbiology Compton
Abstract
Marek's disease virus is a cancer-causing virus of chickens which causes global losses of $US1 billion/year, considerable animal suffering, and which puts at risk free-range poultry operations and possibly wildlife. In commercial poultry operations, the virus has evolved substantially greater virulence over the last fifty years, with previously unseen hyperpathogenic strains now circulating. These rapidly kill unvaccinated birds. It seems extremely likely that something people did to the MDV-chicken interaction prompted this virus evolution; here we seek to find out what. This is an important issue for the poultry industry, which needs to assess the likely direction of future MDV virulence and the evolutionary risk associated with alternative control strategies such new vaccines and genetically enhanced chickens. Preventing further virulence evolution, and even reversing it, would be highly desirable on commercial, ethical and possibly wildlife conservation grounds. While there is little doubt that MDV virulence evolution has occurred, there is very little understanding of which of environmental conditions changed by the poultry industry has been responsible for this evolution. A leading possibility is that it is vaccination. MDV has been subject to vaccination since the late 1960's. MDV vaccines are not sterilising, so that vaccinated birds transmit virus they acquire from their environment. Such 'leaky' vaccination makes viral evolution in immunised populations possible. Theoretical models show that leaky vaccines can prompt virulence increases; the intuition here is that by protecting hosts, vaccines keep virulent pathogens from killing their hosts and therefore themselves. Thus, where they would previously have been removed by natural selection, they can circulate in vaccinated populations. In this proposal, we aim to determine whether this scenario can explain MDV virulence increases. The experimental work will involve comparisons of the evolutionary fitness of MDV strains of varying virulence in vaccinated and unvaccinated birds, and experimental evolution of viral strains through vaccinated and unvaccinated birds. The subsequent data will enable direct testing of the vaccine hypothesis, and other possible explanations of MDV virulence evolution. 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.
Technical Summary
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.
People |
ORCID iD |
Venugopal Nair (Principal Investigator) |
Publications
Baigent SJ
(2013)
Relationship between levels of very virulent MDV in poultry dust and in feather tips from vaccinated chickens.
in Avian diseases
Baron MD
(2018)
Recent advances in viral vectors in veterinary vaccinology.
in Current opinion in virology
Chakraborty P
(2017)
Marek's disease virus infection of phagocytes: a de novo in vitro infection model.
in The Journal of general virology
Kennedy DA
(2017)
Industry-Wide Surveillance of Marek's Disease Virus on Commercial Poultry Farms.
in Avian diseases
Mwangi W
(2010)
Regional and global changes in TCRaß T cell repertoires in the gut are dependent upon the complexity of the enteric microflora
in Developmental & Comparative Immunology
Nair V
(2018)
Spotlight on avian pathology: Marek's disease.
in Avian pathology : journal of the W.V.P.A
Read AF
(2015)
Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens.
in PLoS biology
Description | We showed that the evolution of virulence of Marek's disease virus is driven possibly by leaky vaccines that did not prevent virus shedding. This study highlighted the concept of the potential of vaccines in driving virus virulence |
Exploitation Route | Further studies are needed to test the functions of other generations of vaccines in driving virulence. Choice of new vaccine candidates should also include their ability to reduce virus shedding |
Sectors | Agriculture Food and Drink |
Description | Defining the cistrome and quantitative transcriptome of virus-transformed cells 12. BB/I014284/1 'Defining the cistrome and quantitative transcriptome of virus-transformed cells'- New grant funded by BBSRC April 2012- March 2015 (£548K). |
Amount | £548,000 (GBP) |
Funding ID | BB/I014284/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2012 |
End | 03/2015 |
Description | Studentship on Neurovirulence factor |
Amount | £96,000 (GBP) |
Funding ID | BBS/E/00001833 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2013 |
End | 09/2017 |
Description | Global Alliance for Research on Avian Diseases |
Organisation | Global Alliance for Research on Avian Diseases |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | This alliance led by Pirbright has participation from over 40 countries and comprises of academics and industry professionals. This forum helps in working together, identifies the challenges and opportunities for improved control of avian diseases |
Collaborator Contribution | Two successful international meetings were organised as part of this alliance, one in London in 2015 and most recent one in Hanoi, Vietnam in January 2018 |
Impact | Organisation of two successful international meetings and development of significant collaborations |
Start Year | 2015 |