Infectious bronchitis vaccines: study highlights the need for targeted genetic modification of viruses
Scientists at The Pirbright Institute have shown that Infectious bronchitis virus (IBV) vaccines produced in eggs have unpredictable mutations which may be prone to reversion in the field.
Live attenuated vaccines, where IBV is weakened so that it causes less severe or no disease, are used in the field as they offer better protection compared to other types of vaccines. The vaccine virus is generated by infecting eggs and allowing the virus to grow, removing it and infecting another batch of eggs, and so on sequentially until the virus is sufficiently weakened. However, little is known about how this method of attenuation affects the virus genetically and therefore the mechanisms by which it is being weakened.
The team compared IBV genomes that had been passaged through eggs over 100 times to find out which genes are involved in weakening the virus. They discovered that mutations occurred throughout the IBV genomes, but only 9 mutations were found more than once across the viruses.
“This shows that using egg passages as a means of creating attenuated IBV vaccines produces unpredictable changes in the virus”, said Dr Erica Bickerton, Head of the Coronaviruses Group at Pirbright. “The presence of so few consistent mutations that may weaken the virus indicates the risk that a vaccine strain generated this way could revert back to a more virulent form in the field.”
The team’s research, published in the Journal of Virology, reinforces the need for more targeted genetic modification of IB vaccine viruses to ensure that the changes are both reliable and achieve the best protection. “We will use the mutation hotspots that we have identified in this study to inform the development of live attenuated vaccines that are genetically modified in the lab”, added Dr Bickerton.
Article: Oade, M., Keep, S., Freimanis, G., Orton, R., Britton, P., Hammond, J., Bickerton, E. (2019). Attenuation of infectious bronchitis virus in eggs results in different patterns of genomic variation across multiple replicates. Journal of Virology, online 1 May 2019, doi: 10.1128/JVI.00492-19