Using synthetic biology to generate novel vaccines against avian infectious bronchitis virus (IBV)

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Chickens are vaccinated multiple times against poultry pathogens throughout their lives to protect against different diseases. Infectious bronchitis virus (IBV) causes a respiratory disease in chickens making them more susceptible to bacterial infections. In addition to this, chickens infected with IBV gain less weight and produce fewer high quality eggs. It is important to vaccinate against IBV both for welfare and economic reasons. There are a number of problems with the vaccines available against IBV. There are many different strains of IBV circulating around the globe however currently available vaccines do not cross-protect against all strains. New vaccines are produced by growing a virulent strain of IBV in hen's eggs multiple times. This reduces the pathogenicity of the vaccine strain when it is given to chickens but it increases the pathogenicity of the vaccine strain for chicken embryos. Vaccines against IBV are administered by spraying poultry flocks with the vaccine or by putting the vaccine in the drinking water. It is hard to guarantee that each chicken has received the same dose, which make the vaccines less effective.We have rationally attenuated three strains of IBV using molecular tools. These strains have not been adapted to grow in eggs so are less pathogenic for chicken embryos. This study proposes to establish whether the rationally attenuated strains of IBV could be used as vaccines, by testing the safety, stability and efficacy of all three potential vaccine strains. These novel vaccines have the potential to be given to chicks while they are still developing in the egg so that the chicks are protected against IBV infection even before they hatch. This would guarantee that each chick received the same dose of vaccine and reduce the possibility of vaccine breakdown, which would be very beneficial to the poultry industry. Safer and more efficacious vaccines against IBV will reduce the amount of antibiotics given to chickens to treat secondary bacterial infections resulting from IBV infection. The prolific use of antibiotics in farming may contribute to the development of antibiotic resistance in bacteria, a potentially devastating problem.The second part of the study proposes to use molecular tools to insert the surface protein, the spike, from a different strain of IBV into one of the novel vaccine strains. The spike is the major structure on the outside of the virus that chickens develop antibodies against. It is highly variable between different strains of IBV so antibodies produced against one strain of IBV may not cross-protect against a new strain of IBV. The spike of one of the most economically damaging strains of IBV will be inserted into a vaccine strain. We will assess whether vaccinating with these recombinant viruses is able to protect against challenge with pathogenic virus containing the same spike or with a different spike. We will establish whether the two viruses containing different spikes are able to grow in competition with each other in eggs. This will investigate the potential to vaccinate eggs with both viruses; protecting against two or more important strains of IBV in a single dose.The overall aim of this study is to use synthetic biology to generate a new generation of safer, more efficacious vaccines against the important poultry pathogen, infectious bronchitis virus.