Pirbright strategy priorities brochure

Science Strategy 2015-2020 The Pirbright Institute provides the UK with capacity to predict, detect, understand and respond to incursions of specific high-consequence viral pathogens of livestock, and viruses that spread from animals to humans.

Preventing and controlling viral diseases

Prediction Monitoring the worldwide spread of viral diseases to identify threats to economic prosperity and health, and providing an early warning to the UK and EU of encroaching viral threats Controlling pathogens inside and outside the UK Integration of reference laboratories with fundamental and applied research Predicting pathogen incursion routes Leading and contributing to international disease control networks Capacity building in developing countries Resolving the epidemiology of virus outbreaks

Detection Acting as a key UK and global leader in the detection, containment and elimination of high-consequence viral diseases Pathogen discovery and monitoring Diagnostic test development and validation Translating research findings into commercial methods of detection Monitoring the presence of viruses in livestock, wildlife and vectors Differentiating vaccinated and infected hosts in endemic regions Carrying out mass surveillance during and after virus outbreaks

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Preventing and controlling viral diseases www.pirbright.ac.uk

Understanding Addressing key questions in fundamental science, and identifying the key gaps in our knowledge of the biology of viruses of economic importance Characterising virus structure, genetics, replication and evolution Exploiting genetic, genomic and proteomic data to understand virus and host function Pinpointing factors influencing vector capacity from the laboratory to field Understanding routes of transmission of viruses between hosts Dissecting virus-vector and virus-host interactions

Responding Controlling and eliminating viral diseases through development of vaccines, control of insect vectors, predictive modelling and other measures Providing vaccinology expertise to both academic and industrial projects Developing new control measures and advice for stakeholders Advising disease control agencies including OIE, EU and Defra Providing primary diagnostics during virus outbreaks

Preventing and controlling viral diseases www.pirbright.ac.uk

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Strategic priorities

To identify, contain and eradicate economically important viral diseases of livestock which are present in, or threaten, the UK

To research and survey high consequence livestock and zoonotic virus diseases which are present in, or threaten,

the UK To act as an international hub for disease surveillance to provide an early warning of possible disease incursions

To carry out fundamental research into virus genetics, virus-cell interactions, arthropod-virus interactions, disease pathogenesis, and livestock and avian immunology and vaccinology

To control livestock and zoonotic virus diseases by the development of vaccines, antivirals, diagnostics, genetic selection, genetically modified animals and athropod vectors, and the modelling of disease outbreaks

To provide national facilities and expertise in high bio-containment laboratories, insectaries, animal facilities and collections of vectors and viruses which are accessible to the UK academic and commercial communities

Capabilities Expertise in studying and responding to virus diseases Bio-containment facilities (for laboratory and

in vivo studies) International Reference Laboratories with ISO17025 accreditation

Inbred lines of animals, collections of arthropod vectors and viruses

Detailed understanding of pathogenesis and the host

responses to infection

Insectary facilities for mass production and contained infection with pathogens

High bio-containment engineering and biosecurity expertise Next generation sequencing and in vitro bio-imaging

in high containment Bioinformatics

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Preventing and controlling viral diseases www.pirbright.ac.uk

Major stakeholders Biotechnology and Biological Sciences Research Council (BBSRC) UK Department for the Environment, Food and Rural Affairs (Defra) Wellcome Trust, Medical Research Council (MRC) and other UK research funding agencies

International funding and disease control agencies, such as OIE, WHO, the European Commission, Bill and Melinda Gates Foundation Industrial producers of veterinary vaccines and antivirals Farmers and livestock keepers

Key contacts Prof John Fazakerley, Director of The Pirbright Institute Dr Bryan Charleston, Director of Science Prof Venugopal Nair OBE, Head of Avian Viral Diseases Programme Prof Peter Mertens, Head of Vector-borne Viral Diseases Programme Dr Terry Jackson, Head of Livestock Viral Diseases Programme (Acting) Dr Simon Carpenter, Head of National Capability Grant Programme Dr Michael Rogers, Head of Science Administration

Our mission Research and surveillance to prevent virus diseases of livestock and virus transmission from animals to humans.

Preventing and controlling viral diseases www.pirbright.ac.uk

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Our deliverables : Years 1-2

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Output

Outcome

Evaluate lumpy skin disease vaccines (LSDV) and establish correlates of protection. Models of continental-scale-spread developed for LSDV.

Compare currently available LSD vaccines and establish pathway to design improved vaccines.

Study of bluetongue virus (BTV) genome reassortment in Europe, establish sequence database of orbivirus molecular epidemiology studies.

Identify high risk BTV viruses in Europe to select vaccines and inform control programmes.

First draft of the genome sequence for any Culicoides species.

Identification of Culicoides genes controlling BTV vector competence.

High quality publications on host pathogen interactions.

First multi-state survey of Culicoides in India contributing to understanding BTV transmission.

Improved targeting of techniques used to ameliorate BTV outbreaks in India.

Gene deletion of African swine fever virus (ASFV) results in an increase in IFN beta production that correlates with virus attenuation and induction of protection against challenge in pigs.

First effective prototype vaccine for ASFV developed.

Demonstrate MVA-VP2 vaccines are protective for African horse sickness virus (AHSV), protection associated with virus neutralizing antibodies.

First effective prototype vaccine for AHSV developed.

High-throughput viral genome sequencing, bioinformatics and mathematical modelling to study foot-and-mouth disease virus (FMDV) evolution.

Monitoring FMDV spread, vaccine selection, facilitate studies on the influence of vaccination on virus evolution.

Recombinant FMDV empty capsid vaccines with improved physical stability can be produced in insect cells.

An effective vaccine against FMDV that does not need high containment facilities for production.

Viral vectors have been utilized for immunogenicity studies in target species. For example, chimp adenovirus (ChAdV) expressing human respiratory syncytial virus (RSV) F, N & M2-1 proteins; haemagglutinin of peste des petits ruminants virus (PPRV) completely protects goats.

DIVA compatible vaccines against livestock diseases, with proof of principle for human vaccines.

Aerosol delivery of a candidate universal swine influenza (SI) vaccine results in improved protection.

Demonstrate immune responses can be enhanced by alternative delivery platforms.

Select antibody light and heavy chain pairs by deep sequencing cattle transcriptome. Identify FMDV cross serotype protective epitopes.

Establish experimental and bioinformatic pipeline to select antibodies epitope identification.

Mobile PCR equipment and optimised new isothermal amplification protocols for rapid field diagnosis of FMD.

Provide the UK and Europe with rapid response to disease incursion and diagnostic capacity to endemic countries with limited laboratory facilities.

Development of recombinant infectious bronchitis virus (IBV) vaccine for in ovo use.

To provide the poultry industry with a greater range of vaccines for in ovo use.

Novel herpesvirus-based recombinant vaccines against avian influenza, increased expression of the protective HA antigen.

Provision of an alternative effective vaccine delivery platform.

Identify mechanisms of maintenance of latency/oncogenicity of Marek’s disease virus in lymphoid cells.

Provision of novel strategies for abrogating latency and oncogenesis.

Examine the role of accessory proteins of avian coronaviruses in pathogenesis.

Apply the knowledge on the functions of accessory proteins to generate attenuated vaccine strains.

Transformation plan and training for staff introduced.

Embed organisational humility throughout the Institute.

Develop public engagement materials to broaden topics covered.

Increase the areas of our science communicated at public engagement events.

Improve staff engagement with commercial organisations, in particular the promotion of collaborative and contract work with commercial entities.

Increased staff participation in commercially sponsored research and/or activities.

Improve knowledge exchange activities to encourage external stakeholder engagement and participation in the Institute’s knowledge exchange and commercialisation activities.

Establish regular knowledge exchange activities in the Institute at key events and with other stakeholders.

Our deliverables : Years 3-4 Output

Outcome

Further develop methods to modify arthropod genomes.

Vector control pilot studies using genetically modified arthropods.

RNA/RNA packaging signals conserved across the orbivirus genus and related virus genera, a newly discovered step in the replication cycle.

Prototype live attenuated vaccines developed for double stranded RNA viruses.

ASFV proteins recognised by the porcine immune system identified and used to vaccinate pigs.

Cocktail of candidate proteins used to vaccinate pigs against ASFV as alternative prototype vaccine.

ASHV vaccine undergoing commercial development.

First ASFV vaccine under development.

African buffalo identified as a reservoir of foot-and-mouth disease virus (FMDV) for farmed livestock.

New epidemiological information to aid control of FMDV at the wildlife/ livestock interface. Inform risk assessments for regulation of trade.

Identify new FMDV vaccine master seed stocks for East Africa from banks of field viruses using stability assays and improved vaccine matching protocols.

Partner with commercial company to establish a FMDV vaccine production facility in East Africa.

Establish practical methods to induce mucosal immunity in pigs using aerosol delivery.

Enhance vaccine induced protective immune responses in pigs.

Establish swine T cell clones and define epitopes recognised during SI infection or immunization.

Establish platform to identify protective antigen for vaccine design. Develop reagents to interrogate local immune responses.

Assembly and characterisation of the first cattle Natural Killer (NK) and Major Histocompatability Complex (MHC) class I gene complexes and establish the extent and location of the polymorphism within these highly variable gene complexes.

High resolution genomic markers to allow more precise selection of disease resistance/resilience traits.

In collaboration with the Meteorological Office develop detection systems to identify viruses in aerosols for rapid field diagnosis.

Rapid non-invasive and remote sensing devices to detect pathogens in the field before transmission to neighboring premises.

Antiviral activity of chicken interferon transmembrane proteins (IFITMs): potential of exploiting the use of IFITMs in avian virology and vaccine production.

Improved tools for genetic selection of disease resistant birds and transgenesis.

Identify virulence determinants of avian influenza virus: PA and NS gene segments as well as PB1F2 are major virulence factors of the virus.

Knowledge used to develop safe live attenuated vaccines and diagnostic tests to identify the emergence of virulent strains.

Update and review the Personal Performance and Development Review (PPDR) process/forms and return the reporting year to align with the budgetary year.

Improve the quality of individual objectives and review and thereby improve performance management.

Deliver in-house public engagement/science communication and plain English training.

Increase the number of staff participating in public engagement activities.

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Our deliverables : Year 5 Output

Outcome

Commercial production of FMDV empty capsid vaccine.

Improved control of FMDV in endemic countries and as a biodefence. Next generation of vaccines based on this platform under development, duration of immunity, designing methods to induce cross protection.

ASFV vaccine under commercial development.

A control measure, other than widespread culling, is available for ASFV. Further programmes to develop vaccine, e.g. cross protective vaccines.

High throughput platform established to interrogate the protective antibody response to a range of pathogens in livestock species. Inbred cattle, pigs and poultry used to identify protective T cell epitopes to range of pathogens.

Protective antigen discovery platforms established to inform vaccine design for livestock.

Understanding in more detail the embryonic immune system in poultry.

In ovo vaccination or passive immunization becomes a possibility for a greater range of pathogens.

High definition maps of immunogenetic loci of livestock species developed.

Improved genetic selection for disease resistance and vaccine responsiveness, especially breed/individual variation.

Development of vaccine delivery platforms.

Impact on vaccine efficacy for livestock and proof of principal studies for humans.

Develop tools, components and strategies for genetic management of insect pests. Conditional-lethal genetic systems for new pests, reduced-vector-competence traits and gene insertion methods.

Reductions in competent vector populations to enhance disease control, for example vector-borne viruses.

Improve the working practices in place to enable the promotion of women in science at the key transition points.

An improved number of female scientists in senior posts.

A wide ranging public dialogue programme established to discuss virus disease research.

Informs our research direction and strategy.

Leverage funding for the Enterprise M3 joint research facility.

Secure new grants and collaborations.

The Pirbright Institute receives strategic funding from BBSRC

Cover photo courtesy of HDR Architecture, Inc.; Š 2014 James Brittain

The Pirbright Institute : Preventing and controlling viral diseases Ash Road, Pirbright, Woking, Surrey GU24 0NF t: +44 (0)1483 232441 f: +44 (0)1483 232448 e: enquiries@pirbright.ac.uk www.pirbright.ac.uk