Infectious bronchitis virus: reverse genetics system aids vaccine development
Researchers from The Pirbright Institute working to improve vaccines for infectious bronchitis virus (IBV) have developed a reverse genetics system, based on the pathogenic IBV strain M41, to identify genes which can be targeted for rational attenuation.
Current vaccines for IBV are created by serial passage of virulent IBV field isolates through embryonated hens’ eggs. The different patterns of genomic variation accumulated during this process means that the exact mechanism of attenuation is unknown and presents a risk of reversion to virulence. Additionally, the passaging process adapts the virus to replicate in chicken embryos, increasing embryo lethality. Vaccines produced in this manner are therefore unsuitable for in ovo application.
In research published in the Journal of Virology, Pirbright scientists used a reverse genetics technique to examine how the genetic code influences virus behaviour during infection, which enabled them to then alter the genome of pathogenic IBV strain M41. By altering important genetic sequences, scientists weakened the virus and prevented it causing disease.
Non-structural proteins were identified as potential targets to weaken the M41 IBV strain. The researchers say the study provides evidence that mutations in the genetic code for non-structural proteins offer a promising way to make vaccines against IBV. These vaccines also show potential for in ovo application.
Dr Erica Bickerton, head of the Coronaviruses group at Pirbright said: “The development of this reverse genetics system provides a powerful tool for future in-depth research into IBV’s ability to cause disease and effect the host immune system, as well as vaccine development. The weakened IBV strain generated from this study shows promise as a vaccine strain because the genetic mechanisms of attenuation are proven to be stable and the ability to cause disease in chickens and eggs reduced. The research demonstrates the safety of vaccinating eggs is advantageous to the poultry industry because vaccinating eggs is easier than flocks of chickens. It provides the ability to control the dose and gives protection at the point of hatching.”
Article: Keep, S., Stevenson-Leggett, P., Dowgier, G., Everest, H., Freimanis, G., Oade, M., Hammond, J. A., Armesto, M., Vila, R., Bru, T., Geerligs, H., Britton, P., Bickerton, E. (2022). Identification of amino acids within nonstructural proteins 10 and 14 of the avian coronavirus infectious bronchitis virus that result in attenuation in vivo and in ovo. Journal of Virology, jvi0205921, advance online publication, doi: 10.1128/jvi.02059-21
[SOURCE: The Pirbright Institute]