Award details

Recognition and control of virus infections

Reference	BBS/E/I/00007031
Principal Investigator / Supervisor	Dr Philippa Beard
Co-Investigators / Co-Supervisors	Dr Dalan Bailey, Dr Carrie Batten, Dr Shahriar Behboudi, Dr Erica Bickerton, Dr Andrew Broadbent, Dr Karin Darpel, Dr Isabelle Dietrich, Dr Linda Dixon, Dr Mark Fife, Dr Wilhelm Gerner, Professor Simon Graham, Professor John Hammond, Professor Munir Iqbal, Dr Christopher Netherton, Professor Satya Parida, Dr Paolo Ribeca, Dr Julian Seago, Dr Holly Shelton, Professor Elma Tchilian, Dr Tobias Tuthill
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	6,248,830
Status	Current
Type	Institute Project
Start date	01/04/2017
End date	31/03/2023
Duration	59 months

Abstract

The activities contributing to this objective examine the underlying basis behind the induction and effector phases of immune responses from pathogen recognition through to virus elimination and the formation of memory responses. These complex and interdependent events can now be explored at a resolution that was previously impossible, owing to recent advances in high throughput screening methods, recombinant technologies and imaging techniques. The immune responses of the three key species studied at Pirbright (cattle, pigs and chickens) will all be examined at the molecular and cellular level during natural viral infection and vaccination studies. This will include the use of inbred and transgenic chickens, as well as our inbred pigs and major histocompatibility complex (MHC) homozygous cattle. As these species are the natural viral hosts, our studies have the potential to immediately inform strategies that improve the duration and broaden the efficacy of current vaccines as well as underpin the rational design of the next generation of vaccines. Viruses have evolved an array of strategies to favourably influence host responses after infection. After cell entry, viruses influence innate and adaptive responses by interfering with multiple intracellular and intercellular pathways, for example proteins of many viruses inhibit specific immune recognition mechanisms. Our work in the natural hosts using well characterised and recombinant viruses will establish how different viruses can alter both immune activation and regulation pathways. T and B cells are the major effector cells of the adaptive immune system being able to distinguish between self and pathogens, mount a specific response and reside after the infection to provide immunological memory. Vaccines remain by far the best method to control viral diseases. Consequently T and B cell receptor diversity and their protective roles are a major component of research activities at Pirbright during infection and vaccination. Decades of existing work with influenza and human immunodeficiency viruses has demonstrated that even antigenically variable viruses possess conserved, broadly neutralising antibody eliciting epitopes, but that they are weakly immunogenic. Many of the viruses studied at Pirbright possess regions of high antigenic variability and dominant epitopes that don’t induce broadly neutralising antibody responses. However, it is now clear that sub dominant epitopes and cross-reactive epitopes exist with enormous potential to inform vaccine antigen engineering to boost immunogenicity. Among potential candidate vaccine antigens for each pathogen only a minority induce protective immunity. Therefore, the identification of protective B and T cell antigens and epitopes is crucial for vaccine development and for evaluation of their immunogenicity and efficacy. We will identify and characterise T and B cell antigens and epitopes derived from a range of veterinary species and their viral pathogens, focussing on identification of conserved antigenic targets that may provide broad cross-protection. The immunogenicity and efficacy of vaccines is both quantitatively and qualitatively dependent upon the delivery system used. We will evaluate delivery platforms including virus-like particles (VLP), empty capsids, nanocarriers, viral vectors or live attenuated viruses to improve the immunogenicity and efficacy of vaccines. The combination of vaccine vector technology and targeted delivery of antigen-antibody fusions will facilitate delivery of protective antigens and induce robust humoral and cell-mediated immunity against target viruses.

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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