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Studies on Avian Infectious Bronchitis Virus to underpin the development of Stable Technologically Advanced Vaccines for more effective sustained control. - OD0717

Description
A report commissioned by Defra demonstrated that not only is infectious bronchitis (IB) a major cause of ill health amongst chickens, it is also responsible for more economic loss in the UK poultry industry than any other disease. The virus responsible is a coronavirus (IBV). It causes not only respiratory disease but also damage to the egg-producing organs of hens, and to kidneys.

IB is partly controlled by live vaccines, i.e. by virus that still grows in chickens but which has been weakened (attenuated) so that it no longer causes disease. This is done by growing virulent virus scores of times (passage) in hens` eggs. Eventually mutations arise by this rather haphazard method, some of which lead to attenuation of the virus – it no longer causes disease. Viruses of many types that are attenuated by the passage approach have only a few mutations that are responsible for their lack of virulence. Once given to animals, some vaccines back-mutate, becoming virulent again, which is clearly undesirable. We have a procedure whereby we can make big changes to the virus that cannot be reversed when IBV vaccine is applied to chickens. This procedure involves removing genes from the virus.

The genes of IBV occur in a single piece of genetic material, the genome, analogous to a chromosome. However, whereas chromosomes are made of DNA, the IBV genome is made of RNA. RNA is very difficult to modify, so we have made a copy of the IBV genome in DNA form, which is much more amenable to modification.

We have already made a DNA copy of an attenuated, non-disease-causing strain of IBV called Beaudette. We have been studying two IBV genes (3 and 5), each of which encodes two small proteins (3a, 3b, 5a, 5b). We have produced modifed IBVs that do not make one or other of these proteins. The mutants still grow normally in the laboratory. Other coronaviruses have got small proteins of unknown function, though they are very different from those of IBV. Interestingly, when some of these genes were removed from other coronaviruses the viruses still replicated but no longer caused disease. This showed that removal of these genes has potential for attenuating virulence to produce vaccines that could not revert to virulence. By analogy, it is possible that removal of one or more of the 3a etc. proteins of IBV will be a means of producing IB vaccines that would be unable to revert to virulence.

To test this approach we need to have a DNA copy of the genome of a virulent strain of IBV, from which we shall methodically remove genes 3 and 5. A large part of this proposal is the construction of this DNA copy.

A major contributory factor to the detrimental impact of IBV on poultry is that it exists in many forms. Although a chicken will become immune following infection with one form of IBV, that immunity does not protect it adequately against other forms. A large protein at the surface of the virus, the spike protein, is responsible for the different forms of the virus. We have replaced the spike protein gene of our Beaudette strain with that from a very different form of IBV. We want to see if vaccinating chickens with this modified IBV will provide good protection against this different form of IBV. A successful outcome would indicate that designer IB vaccines could be made in this way.
Objective
This project comprises three objectives:

1. Progress towards identifying IBV proteins that determine pathogenicity/attenuation.
2. Will the expression of the spike protein gene of the nephropathogenic B1648 strain from a recombinant IBV induce good protection against challenge with B1648?
3. Will incorporation of the spike protein gene of the nephropathogenic B1648 strain into the genome of the non-pathogenic Beaudette strain make the latter nephrotropic and nephropathogenic?

Objectives 1 addresses objectives (a) and (b) of the Defra Research Requirements Document of 2005 in respect of the area Coronavirus in Poultry: (a) attenuating the pathogenicity of the virus in a non-reversible way while maintaining or enhancing immunogenicity; (b) attenuation of the virus to allow in ovo application. Objectives 2 and 3 address Defra objective (b) and also (c) - creation of a system for the rapid swapping of spike protein immunogens for the induction of immunity to new serotypes.
Time-Scale and Cost
From: 2006

To: 2010

Cost: £694,761
Contractor / Funded Organisations
Institute for Animal Health (BBSRC)
Keywords
Animal Diseases              
Animal Health              
Biotechnology              
Control              
GM Food              
Neoplastic              
Pathogenesis              
Plants and Animals              
Poultry              
Fields of Study
Animal Health