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Transmission and Vaccine-Induced Protection of Marek's Disease - OD0722

Description
Marek’s disease (MD), caused by the highly contagious Marek’s disease virus (MDV), remains a major challenge affecting poultry health. Defra funding in the past for MD research was valuable in identifying a number of distinct aspects of MD and maintaining expertise in MD research in the United Kingdom. As part of our research, we have gained significant insights into MD. For example, we have identified several genes, including the MEQ gene and some of the MDV-encoded microRNAs which are directly associated with the induction of cancer. The manipulation of the viral genome to introduce deletions or mutations was possible through the development of infectious bacterial artificial chromosome (BAC) clones of the virus. We have also demonstrated in preliminary studies that viruses deleted in the MEQ gene as well as viruses with deletions of some of the microRNAs can be used as vaccines against virulent MDV. In this project, we want to extent these preliminary studies to examine the efficacy of these viruses as vaccines against different pathogenic virus. Moreover as most of the commercial birds are derived from vaccinated hens and thus have maternal antibodies at hatch, we also want to examine the efficacy of such molecularly-modified vaccines in maternal antibody-positive birds.
Until recently, the poultry industry relied mostly on the use of a plethora of live attenuated or inactivated vaccines for the control of infectious diseases. However, there has been an increasing trend in the use of recombinant vectored vaccines, and it is likely that the control of more and more avian diseases will be achieved through the use of recombinant vaccines. Majority of the commercially used recombinant vaccines use the fowl pox virus (FPV) or the herpesvirus of turkeys (HVT) as the vectors. As a virus capable of persisting latently in the vaccinated hosts, HVT-vectored vaccines have been shown to provide long-term protection. In addition to HVT, SB-1 and Rispen’s (CVI988) strains of herpesviruses are also used as vaccines by the poultry industry. However, these strains have not been widely exploited as recombinant vectors. We have previously reported the construction of infectious BAC clones of HVT, SB-1 and CVI988, and have recently shown that HVT BAC clones could be easily manipulated to express foreign genes. In this proposal, we want exploit the use of SB-1 as a recombinant vector against viruses such as IBDV and NDV.
MD vaccines, except HVT, are only available as ‘wet vaccines’ to be transported in liquid Nitrogen. This is because these vaccines are cell-associated and the infectivity relies on the use of live infected cells for vaccination. HVT on the other hand, can produce cell-free virus at least partially, and hence is also available as freeze dried ‘dry’ vaccines. As part of the previous project, we have identified the association of some of the HVT glycoproteins in cell-free virus production. We want to explore the functions of these glycoproteins in order to understand the determinants of cell-free virus production, and examine the possibility of developing novel cell-free viruses with the serotype 1 MDV.
Objective
1. Examine whether novel molecularly-defined vaccines be derived from Marek’s disease vaccine strains deleted/mutated in oncogenic determinants.
2. Exploit the bacterial artificial chromosome (BAC)-mutagenesis strategies to develop novel SB-1 strain-based recombinant viral vaccines expressing protective viral genes from selected avian pathogens.
3. Identify the determinants of cell-free virus production in avian herpesviruses and examine the prospects of developing novel vaccines from MDV-1 vaccine strain.
Time-Scale and Cost
From: 2013

To: 2016

Cost: £890,330
Contractor / Funded Organisations
IAH - Institute for Animal Health
Keywords
Animal Diseases              
Poultry              
Fields of Study
Animal Health