Identification of cross-specific epitopes on FMDV capsids
Foot-and-mouth disease (FMD) is a highly contagious, acute viral disease of cloven-hoofed, domesticated and wild animals, with the potential to cause enormous economic losses. Using tools and expertise that are available through the Pirbright Antibody Hub, and by engineering stabilised FMDV capsids from several serotypes, we aim at sequencing, expressing and characterizing cross-protective antibodies against FMDV and identify viral capsid epitopes that will enhance a cross-protective response. These data will immediately inform a second generation of capsid vaccine design and present new opportunities to better define the protective element of a polyclonal response and the frequency and function of B cells that ultimately induce a widely cross-protective response.
Development of a pig model for influenza study
We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing monoclonal antibodies (mAb). We have generated porcine influenza specific mAbs which recognize similar epitopes to humans, showing that pigs will be very useful to predict the evolution of influenza viruses. Treatment with pig mAbs reduced viral load and lung pathology after in vivo influenza virus challenge. The model will allow us to investigate how best to use mAbs to prevent or treat severe influenza disease. We will compare the therapeutic effects of mAbs with different specificity and the synergistic effect of cocktails of mAbs, evaluate antibody delivery platforms, the effect of IgA and different IgG subclasses and the role of Fc mediated functions.
Improving HVT-based vaccines for poultry rearing
Poultry rearing is a major contributor towards the provision of both income and livelihood for many Low- and Middle-Income countries. Sustainability of poultry production is constantly under threat due to several infectious diseases, such as Newcastle disease. Poultry producers are increasingly using recombinant vectored vaccines in the fight against these diseases and herpesvirus of turkey (HVT) is one of the most successful viral vectors used for protection against multiple avian diseases. As part of the Hub, we will aim to improve the HVT-based vaccine by generating multivalent vectors expressing improved viral antigens capable of inducing stronger and broader immunity. We will use these improved vectored vaccines for antigen discovery using B-cell sequencing strategies developed by the Hub.
Engineering recombinant infectious bronchitis viruses (IBV) to identify cross-reactive epitopes on the spike glycoprotein
Avian coronavirus infectious bronchitis virus (IBV) causes an acute, highly contagious respiratory disease of poultry that is of both welfare and economic importance to the global poultry industry. Infected chickens gain less weight and produce fewer, good quality eggs. Several serotypes and genotypes of IBV co-circulate in poultry flocks, however, vaccination against one serotype often offers limited cross-protection against another serotype. Using tools and expertise that are available through the Pirbright Antibody Hub, we are dissecting protective antibody responses against IBV and aiming to identify conserved epitopes between different IBV serotypes. These data will be used to develop broadly cross-protective vaccines against different IBV serotypes.
Prevention and control of avian influenza in poultry through passive immunization.
Multiple subtypes (H5, H6, H7 and H9) of avian influenza viruses (AIV) are causing severe global losses to both commercial and backyard poultry as well as posing credible zoonotic and pandemic risk to humans. Current disease control systems including culling of infected and potential contact poultry flocks, movement restrictions and vaccination have shown limited success. Therefore, there is an urgent need for novel and more cost-effective disease control tools, which could provide faster and more robust protection of chickens against multiple AIV subtypes. This is particularly important bearing in mind a short life span (up to 40 days) of broiler chickens, which constitute 80% of poultry flocks and are often left unvaccinated due to relatively long time of an immune response development after immunization. To overcome this challenge, we are developing a passive immunization approach as immunoprophylaxis by engineering single-chain variable fragments (scFv) monoclonal antibodies into a multivalent format, for delivery via HVT and NDV viral vectors. This will be administered to chicken embryos before hatching (in ovo vaccination) in addition to mature chickens via an aerosol delivery system.