Pirbright study may reduce reliance on embryonated hens’ eggs
Scientists at The Pirbright Institute have identified a promising new route to develop faster, more adaptable vaccines against infectious bronchitis virus (IBV), one of the poultry industry's most economically significant diseases.
Researchers have shown that a protein from an attenuated laboratory strain of IBV can both weaken highly pathogenic virus strains and enable them to be grown in cell culture, a breakthrough that could reduce reliance on embryonated hens' eggs for vaccine production and accelerate responses to emerging variants.
IBV, a coronavirus that infects chickens, causes a highly contagious disease characterised by respiratory illness, reduced growth, and declines in egg production and quality. Some strains can also spread beyond the respiratory tract, causing kidney disease and significant losses for poultry producers worldwide.
Live attenuated vaccines are currently produced by repeatedly passaging virulent virus strains through specific-pathogen-free embryonated hens' eggs, a process that can require over 80 passages and take considerable time. The approach remains dependent on a supply of disease-free eggs and can struggle to keep pace with the emergence of new viral strains.
In a new study, published in the Journal of Virology, Pirbright researchers investigated whether the spike protein from the attenuated IBV strain Beaudette could provide a universal approach to vaccine development. Using reverse genetics, they replaced the spike gene of a nephropathogenic, disease-causing IBV strain known as D388 with the corresponding gene from Beaudette.
The resulting recombinant virus was able to grow efficiently in Vero cells, a cell line widely used in the manufacture of licensed human and animal vaccines. Importantly, the modified virus also exhibited a markedly attenuated phenotype in chickens, causing fewer clinical signs while retaining genetic stability.
James Kirk, lead author of the study, said: “Our findings show that the Beaudette spike protein can both attenuate a highly pathogenic infectious bronchitis virus strain and allow it to be grown in cell culture. This opens up exciting opportunities for the development of rationally designed vaccines that can be produced more quickly and adapted more readily to emerging viral strains."
The findings suggest the Beaudette spike protein can simultaneously provide two major advantages for vaccine development: rational attenuation of virulent viruses and the ability to propagate vaccine candidates in cell culture rather than relying solely on eggs.
The research also sheds new light on how IBV causes disease.
Although the modified virus was still able to infect similar tissues to the original pathogenic strain, including sites associated with kidney infection, it triggered a significantly less inflammatory immune response. This indicates that disease severity is not determined solely by where the virus replicates in the chicken.
Instead, the study identifies the spike protein as a key contributor to nephropathogenicity, suggesting that the way the virus interacts with the host immune system plays an important role in driving disease.
Analysis of infected chickens revealed that the attenuated virus induced a broader but more controlled innate immune response, while the pathogenic strain generated a stronger and more prolonged inflammatory reaction associated with tissue damage.
The researchers believe the findings could have important implications for the future control of infectious bronchitis.
The study demonstrates that the Beaudette spike protein can transfer both cell-culture growth capability and attenuation to a genetically distinct pathogenic strain, supporting its potential as a broadly applicable tool for next-generation IBV vaccine development.
By reducing dependence on embryonated eggs and enabling more rapid production of vaccine candidates, the approach could help strengthen disease control programmes and improve the poultry industry's ability to respond to emerging infectious bronchitis threats.
Read the paper: Kirk J, Sives S, Rayment A, Tappin A, Jones S, Miles J, Tennakoon C, Martin-Drew E, Freimanis G, Francis H, Peacock TP, Sutton K, Webb I, Davidson AD, Britton P, Bickerton E, Keep S. Spike protein derived from an apathogenic IBV strain confers attenuated phenotype to a nephropathogenic IBV strain. J Virol 0:e01103-26.