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Studies on avian infectious bronchitis for safe, technologically advanced vaccines for long-term sustainable control - OD0714

Description
Infectious bronchitis (IB) is the major respiratory disease of the domestic fowl amongst the nearly one billion chickens present annually in the UK. Manipulation of the IB virus (IBV) genome has the potential of producing better vaccines in a rational and timely manner: genetically stable i.e. not reverting to virulence; less interference between two IB vaccines given concurrently; genetically marked to aid diagnosis and epidemiological studies. The main objective of this project is to assess the effects on pathogenicity of specific, well-defined alterations to some of the IBV genes. This will also increase our understanding of the role of a number of the IBV proteins in the disease process. It is hoped to identify genetic alterations that will attenuate pathogenicity in an irreversible manner whilst retaining good growth during vaccine preparation. This work will address the DEFRA policy of reducing mortality amongst poultry; increasing bird welfare; decreasing the use of chemotherapeutics to control disease by increasing the efficiency of disease control by improved vaccination; promoting sustainable production systems. This strategic research is aimed at identifying useful generic changes that can be made to IBV genomes such that vaccine manufacturers can later apply them, to make the next generation of IB vaccines, for use by poultry producers.
Objective
01 The Beaudette strain of IBV, after >300 passages in domestic fowl embryos, is non-pathogenic for chicks and highly pathogenic for embryos, the reverse of the situation with the original Beaudette isolate and other field isolates. Are the mutations that have contributed to this change located in gene 1 (replicase) or in one or more of the other genes? A chimaeric full-length clone will be made to answer this question, with gene 1 from Beaudette and all other genes from M41 (pathogenic for chickens). If rIBV is recovered from this clone and is pathogenic for chicks, it will also be used in objectives 03, 05 and possibly in 06. If the rIBV is not pathogenic for chicks, gene 1 of M41 will be cloned outwith this project and used to construct a full-length clone, outwith this project, comprising totally M41 sequence. (We already have genes 2 to the 3’ end in cloned form). 02 Does the swapping of the S gene of strain Beaudette (highly pathogenic for embryos) with that of strain M41 (low pathogenicity for embryos) result in a rIBV that is non-pathogenic for embryos? I.e. to what extent is the pathogenicity of IBV determined by the spike protein? This investigation will be based on our existing Beaudette clone. 03 Does the swapping of the S gene of a strain of IBV that is pathogenic for chicks with that of Beaudette (non- pathogenic for chicks) result in a rIBV that is non-pathogenic for chicks? I.e. to what extent is the pathogenicity of IBV determined by the spike protein? This objective is dependent on obtaining a pathogenic clone from one of the two approaches in 01. 04 Do one or more of the non-structural proteins (3a, 3b, 5a, 5b) affect growth/pathogenicity of IBV in embryos? This will be based on mutations made with our existing Beaudette clone (highly pathogenic for embryos). The stability of the rIBVs will also be assessed, by passaging them. 05 Do one or more of the non-structural proteins 3a and 3b affect growth/pathogenicity of IBV in chicks? If a clone of IBV pathogenic for chicks is obtained [01], selected mutations will be made in gene 3 to study the effect on replication in chicks. 06 Does the single intergenic region (IGR) in IBV have a role in replication/pathogenicity in vivo? Also, can the IGR be modified for the purposes of genetically marking the virus? Modifications to this will made to see if viable virus with unique alterations can be recovered and whether growth in vitro or in vivo has been affected.
Project Documents
• Final Report : Studies on avian infectious bronchitis for safe, technologically advanced vaccines for long-term sustainable control   (183k)
Time-Scale and Cost
From: 2003

To: 2006

Cost: £606,000
Contractor / Funded Organisations
Institute for Animal Health (BBSRC)
Keywords
Animal Diseases              
Animal Health              
Biotechnology              
Control              
GM Non-Food              
Plants and Animals              
Poultry              
Vaccines              
Fields of Study
Animal Health