Engineering vaccines for multiple strains of Infectious Bronchitis Virus

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In new work funded by a Biotechnology and Biological Sciences Research Council (BBSRC) 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.

Vaccination of poultry for IBV would alleviate a major problem for the poultry industry. However, current vaccine regimes based on a single virus group, known as a 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 real need to develop new vaccines against infectious bronchitis (IB) 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, viruses that are made up of parts from different strains. In this case they made 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).

Protecting chicks using a recombinant virus
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 the future vaccines.
To test these and other recombinant viruses further, particularly with regards to their potency, or immunogenicity, as vaccines, Dr Bickerton collaborated with a team at The University of Edinburgh. Professor Lonneke Vervelde, at the Universitys 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.

Giving booster vaccinations might also improve protection
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.
A recombinant vaccine would have great potential for the development of more cost effective and efficient commercial vaccines, easing a significant economic burden on the poultry industry, as well as generating technology that could enable a more rapid response to newly emerging IBV strains.

Infectious Bronchitis Virus
Infectious bronchitis virus (IBV) is a highly infectious avian pathogen, which affects the respiratory tract, gut, kidney and birds’ reproductive systems. It belongs to the Coronavirus family, genus Gammacoronavirus, which has a single stranded RNA genome, surrounded by a nucleocapsid and envelope.

Associated diseases
IBV causes infectious bronchitis, targeting the respiratory and uro-genital tract. IBV mainly causes respiratory disease in the infected birds but also lowers egg production, and can cause kidney damage.

Clinical signs
– Young chickens are depressed and huddle under the heat source;
– Gasping, coughing and nasal discharge;
– Drop in egg production;
– Poor quality eggs; misshapen or soft-shelled eggs with watery content;
– When the kidneys are affected, increased water intake, depression, scouring and wet litter are commonly observed.

Disease spread
IBV is spread by aerosol or by ingestion of contaminated feed, water or faeces. Contaminated equipment and material are also a potential source for indirect transmission over large distances.

Disease prevalence
IBV is globally spread, being prevalent in all countries with an intensive poultry industry.

Source: The Pirbright Institute