Antigenic characterisation of infectious bursal disease virus to improve vaccination strategies and vaccine design

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The poultry industry is essential to securing enough food for the expanding human population. However, infectious bursal disease virus (IBDV), responsible for Gumboro Disease in chickens, is recognised as a worldwide concern for the industry. The disease can be severe and lead to high death rates and suppressed immune responses that can exacerbate other infections. So great is the concern that every year billions of chickens are vaccinated against IBDV and there has been considerable investment into new types of vaccine. Vaccines typically work by stimulating the production of neutralising antibodies that bind the virus and prevent it from entering the host cells. However, despite these developments, numerous vaccine failures have been reported, with some flocks experiencing high death rates, despite being vaccinated, for reasons that are poorly understood. When a vaccine failure occurs, the sequence of the virus circulating in the flock (field strain) is determined and if there are mutations found, it is often presumed that a mis-match between the vaccine strain and the field strain is responsible for the failure. However, while some changes in the virus sequence will cause a vaccine to be ineffective, this is not the case for every mutation, and there are many other potential reasons why a vaccine may fail, including poor timing of vaccination or inadequate dosing. It is therefore important to determine which sequence changes result in vaccine failures and which do not, in order to determine whether a more matched vaccine is needed in a particular region. One way to discern this is to determine the ability of the vaccine to induce antibodies that neutralise the field strain, in so-called 'neutralisation assays'. However, neutralisation assays are not routinely conducted, as field strains of IBDV do not infect the cells that are typically used.Field strains of IBDV infect cells in an organ known as the bursa of Fabricius. Dr Andrew Broadbent at The Pirbright Institute has shown that when cells are removed from the bursa and kept alive in the laboratory, field strains of IBDV will infect and replicate in them. He has used these cells to conduct neutralisation assays with field strains of IBDV in order to quantify neutralising antibodies. In addition, his group has developed IBDV strains that are tagged with a small molecule (GFP11). When the tag interacts with another, larger molecule (GFP1-10), it fluoresces green. Professor Helen Sang's group at The Roslin Institute has developed chickens that contain the GFP1-10 molecule in every cell. A collaboration between the two groups has already shown that cells from these chickens fluoresce green when infected with the tagged IBDV, meaning they can be used in the neutralisation assay to make it higher throughput. We aim to generate a panel of tagged IBDVs from diverse strains from different geographical areas, and use bursal cells containing GFP1-10 to determine whether IBDV vaccines cross-neutralise different IBDV strains. This will help determine the extent to which vaccine failure is due to changes in the virus sequence. Moreover, we will screen the panel of viruses to determine whether certain strains induce antibodies that cross-neutralise others, and we will identify common regions that the antibodies bind to that are shared between the different strains. If we identify common antibody binding sites between strains that cross-neutralise, then it may be possible to develop a more universal IBDV vaccine that can protect against multiple strains in the future.