Towards control of Infectious bronchitis virus; understanding cross protection and genetic plasticity of IBV
Lead Research Organisation:
THE PIRBRIGHT INSTITUTE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
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.
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.
Planned Impact
unavailable
