Recombinant Infectious bronchitis viruses: potential for a new generation of vaccines
Researchers at The Pirbright Institute and The Roslin Institute have published work investigate the role of the infectious bronchitis virus (IBV) spike (S) protein in generating protection through vaccination.
Current vaccine regimes, based on a single serotype, often do not produce sufficient immunity against other serotypes, so two or more different vaccines have to be used in order to provide broader protection. Consequently, there is a need to develop new vaccines against infectious bronchitis that are protective against multiple strains of the virus.
To do this Dr Erica Bickerton, leader of the Coronaviruses group at Pirbright, and her colleagues generated recombinant viruses containing different S proteins. The S protein on the surface of IBV binds to a protein on the outside of cells to initiate entry and infection. The recombinant viruses were made by incorporating different parts of the S protein, known as subunits S1 and S2, from vaccine or virulent IBV strains into a non-pathogenic strain of IBV called Beaudette (Beau-R).
They found the recombinant vaccines were capable of replicating in primary chicken kidney cell cultures and in Vero cells, which are derived from African green monkey kidney cells and are a widely used cell line. This research, published in the Journal of General Virology, implies that recombinant IBVs containing S1 subunits from diverse IBV strains are able to grow in a cell line that may facilitate rational design of future vaccines.
To test these and other recombinant viruses further, particularly with regards to their immunogenicity, as vaccines, Dr Bickerton collaborated with a team at The University of Edinburgh. Professor Lonneke Vervelde, at the University’s The Roslin Institute, who led the study published in the Journal of Virology said: “There is a real need to develop new vaccines against infectious bronchitis that protect against multiple strains and offer rapid responses. We are trying to make a vaccine that offers broad protection, but further research is needed to develop a more robust vaccine.”
Dr Bickerton added: “In this study we found it is possible to partially protect chickens against IB using a recombinant virus vaccine incorporating the S1 or S2 subunits. However, these vaccine viruses did not stimulate an optimal immune response. A better immune response was seen when the full S protein from the virulent strain was incorporated into the Beaudette vaccine virus”.
This suggests that the S protein subunits from different strains do not come together as well as the subunits from a single strain do, which reduces their ability to protect chickens against infection. The implication is that optimal formation of the S protein is required, and it is expected, with further optimisation the researchers will see a greater immune response generated.
The study reported here is part of a larger project looking at specific differences in the S protein between groups of IBV. If some of these differences can be incorporated into a single, effective vaccine strain that will protect against all groups of IBV then this would have great potential for use in the poultry industry.
The next steps are to engineer a recombinant IBV vaccine with improved replication, which may improve the immune response. Giving booster vaccinations might also improve protection. “It is possible that the Beaudette vaccine strain ‘backbone’ for our recombinant viruses was too weak, or attenuated, but the genetic tools we have that allow us to engineer recombinant viruses will enable us to test different backbone strains and S proteins with a view to finding a vaccine strain that will protect against multiple or all groups of IBV,” said Dr Bickerton.
Recombinant infectious bronchitis viruses expressing heterologous S1 subunits: potential for a new generation of vaccines that replicate in Vero cells by Erica Bickerton, Giulia Dowgier and Paul Britton, published in Journal of General Virology, online 24 October 2018, doi: 10.1099/jgv.0.001167
Recombinant Infectious Bronchitis Viruses expressing chimaeric spike glycoproteins induce partial protective immunity against homologous challenge despite limited replication in vivo by Samantha Ellis, Sarah Keep, Paul Britton, Sjaak de Wit, Erica Bickerton and Lonneke Vervelde, published in Journal of Virology, online 12 September 2018, doi: 10.1128/JVI.01473-18
[SOURE: The Pirbright Institute]