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Towards control of Infectious bronchitis virus; understanding cross protection and genetic plasticity of IBV

Reference	BBS/E/I/00001901
Principal Investigator / Supervisor	Dr Erica Bickerton
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	54,558
Status	Current
Type	Institute Project
Start date	06/10/2014
End date	05/10/2018
Duration	48 months

Abstract

Vaccination against numerous endemic pathogens is an essential component of the poultry industry. Without these vaccines chickens would succumb to infection at an early age reducing the productivity of the industry well below sustainable levels. Infectious bronchitis virus (IBV) is an endemic virus that causes severe disease outbreaks in chickens worldwide; affecting the global production of meat-type birds, due to problems in weight gain and quality, and in egg production through decrease in numbers of eggs and egg quality. Effective and economically viable vaccines against IBV are available, but multiple combinations of available vaccines are needed because the level of cross-protection against different IBV strains is insufficient. Poor cross-protection is the result of variation in a major surface protein of the virus (the spike (S) protein). New variant strains of IBV with differences in the S protein appear regularly and, through analysis based on the sequence of the S protein, it is impossible to predict which vaccines will induce protection against the newly emerged viruses. Only elaborate and expensive testing in chickens elucidates which vaccine combination is needed to protect against a new strain of IBV. This study will address the seemingly unpredictable nature of the virus. The availability of a unique reverse genetics system for IBV has potential for developing a new generation of live vaccines. In this proposal we will generate recombinant viruses that are identical except for the immunodominant S1 subunit, of the economically most important IBV strains (M41, 4/91 and QX). Vaccination-challenge experiments with the same and with different viruses will identify that there are different degrees of protection. The cause of an insufficient and unpredictable level of cross protection is the main focus of this study. Ultimately we will determine the key regions or epitopes on the S1 subunit of the economically most important IBV strains that are responsible for inducing protective immune responses. We will use novel epitope fingerprinting technology to determine the key regions that are recognised by the antibodies induced after vaccination. Identification of key regions following vaccination with one IBV strain and after vaccination with multiple strains will allows us to determine which epitopes are needed by a vaccine to induce protection. When new virus strains emerge we will then be able to predict if and which vaccines will be required to induce effective protection against the new virus strain. Moreover, we will further develop our understanding of how pressure from the bird's immune responses on the virus might drive the virus to change or mutate. This will involve the passage of an IBV strain in eggs, in the same way as vaccines are produced. However, the replication of the virus will be put under immune pressure by the addition of antibodies specific for this virus. This will essentially mimic the immune pressure applied on the replicating virus as occurs after vaccination. Using contemporary deep sequencing technology we will identify the molecular changes that occur as a result of immune pressure and the process by which the virus is able to evade the applied vaccine, potentially evolving into a new variant. By understanding and manipulating the processes that govern virus adaptation after vaccination we aim to identify ways of reducing the danger of vaccine strains changing and causing damaging disease outbreaks. Results from this proposal will provide (1) crucial information on why vaccines used to control an important avian endemic pathogen IBV fail to induce cross-protection, (2) information for the efficient use of existing vaccines and (3) the development of more efficient vaccines, thus ensuring that poultry farming remains not only a secure food source but also increases the economic competitiveness of the UK.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Animal Health, Immunology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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