Institute Preventing and controlling viral diseases

Don King [email protected]

About us The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans.

• Working to contain, control and eliminate economically and medically important diseases • Contributing to global food security and health, improving quality of life for animals and people • Combining highly innovative fundamental and applied bioscience • Approximately 250 staff • Annual income ~£29M • £76.9M strategic investment from the UK Biotechnology and Biological Sciences Research Council during 2011-12

Impact: UK economy

Annual contribution of livestock • Foot-and-mouth outbreak to the UK economy 2001 cost UK economy >£2-8bn Game Cattle £1,600M £4,487M • Calf pneumonia costs UK economy £54m p.a. Sheep £628M Poultry • IBV costs UK economy £7,500M £22m p.a. Horses £4,000M • Prediction and rapid Pigs £735M response to bluetongue in 2007 saved economy £0.5bn p.a.

(Poultry data provided by Peter Bradnock (CEO, ) & Mark Williams (CEO, British Egg Industry Council) Our science

Research at the Institute is a synergistic combination of fundamental and applied science, based upon a wide range of expertise, and unique biological and physical resources. The science strategy is delivered through three strategic programmes:

• Avian Viral Diseases • Livestock Viral Diseases • Vector-borne Viral Diseases

Each programme comprises a platform of fundamental science projects that provide the new knowledge that is then translated, within the programmes, into applied science. Institute Strategic Programmes

CSFV FMDV

BVDV RPV LVD

PPRV SIV

ASFV BRSV AIV RVFV ILTV BTV MDV

NSDV VVD ALV-J AVD EEV IBV

WNV AHSV FPV IBDV Interactions between disciplines

Virus biology, gene Diagnostics, disease functions, evolution surveillance, mathematical modelling Virus-host interactions in models in natural hosts Immune responses to Role of arthropod virus vectors in virus & vaccines transmission Role of the Reference laboratories

• Assist in disease emergencies • Strong international links • Provide training and capacity building • New & improved diagnostic tests

• Global surveillance • Risks, threats and tools

Cattle Plague - Rinderpest

The disease that defined modern veterinary science and was instrumental in the founding of the world’s first veterinary schools, the British State Veterinary Service (1850s), the World Organisation for Animal Health (1924), and the FAO Animal Health Service (1946) South Africa: 1896 Translating basic science into tools for disease control: Foot-and-mouth disease (FMD) FMD is a global problem The conjectured status of FMD showing principal virus pools What we do…..

• Tracing sources of outbreaks • Vaccine selection O/CHA/109/2010* (LVRI) O/CHA/84/2010* (LVRI) O/CHA/114/2010* (LVRI) Tracking spread of FMDV O/CHA/117/2010* (LVRI) O/CHA/102/2010* (LVRI) O/SKR/5/2010 O/CHA/57/2010* (LVRI) O/JPN/2010 (NIAH) O/RUS/Jul 2010 (ARRIAH) O/CHA/31/2010* (LVRI) O/CHA/115/2010* (LVRI) O/CHA/79/2010* (LVRI) O/HKN/9/2010 81 O/HKN/7/2010 2 O/CHA/51/2010* (LVRI) O/SKR/4/2010 O/CHA/106/2010* (LVRI) 75 O/CHA/104/2010* (LVRI) O/CHA/72/2010* (LVRI) 6 O/CHA/39/2010* (LVRI) O/HKN/19/2010 O/CHA/64/2010* (LVRI) 135 86 73 O/HKN/6/2010 97 O/HKN/1/2010 152 O/CHA/107/2010* (LVRI) 98 O/CHA/82/2010* (LVRI) 2 O/CHA/80/2010* (LVRI) 89 O/TAI/22/2009 (HQ116269) O/MYA/5/2009 (HQ116228) 85 292 O/MYA/11/2009 (HQ116232) 2 O/MYA/3/2010

86 O/MOG/2004 (ARRIAH) 98 O/HLJOC12/03 (China) (DQ119643) O/MYA/1/2006

3 99 O/MYA/3/2009 O/MYA/2/2006 (HQ116225) O/VIT/5/2010 99 O/TAI/20/2009 (HQ116267) 84 O/MYA/12/2009

97 O/MYA/3/2008 (HQ116227) O/LAO/1/2007 (HQ116175) O/MAY/5/2009 (HQ116213) O/LAO/2/2008 (HQ116180) O/TAI/2/2009 (HQ116257) 2 O/TAI/6/2008 (HQ116253) 3 O/TAI/2/2008 (HQ116250) O/TAI/5/2008 (HQ116252) O/TAI/4/2009 (HQ116259) O/MYA/2/2008 (HQ116226) O/TAI/18/2009 (HQ116265) O/MAY/8/2009 (HQ116216) O/TAI/3/2009 (HQ116258) O/LAO/1/2009 (HQ116182) O/VIT/2/2010 O/TAI/23/2009 (HQ116270) O/TAI/19/2009 (HQ116266) O/MAY/20/2009 (HQ116218)

70 O/TAI/13/2009 (HQ116261) O/TAI/12/2009 (HQ116260) 99 O/MOG/66/2010* (ARRIAH) 74 O/MOG/9/2010 O/MOG/6/2010 O/MOG/77/2010* (ARRIAH) O/MOG/7/2010 O/MOG/5/2010

84 O/MOG/CO3/2010* (ARRIAH) O/RUS/Aug 2010 (ARRIAH) O/MOG/2/2010 O/MOG/1/2010 O/MOG/56/2010* (ARRIAH) O/MOG/4/2010 O/MOG/3/2010 East Asia incursions: 2010-2011 (O/SEA/Mya-98) O/TAI/189/87* (TRRL) Complete FMDV sequences can resolve farm-to-farm spread Bulgaria: 2011 Full genome sequence data generated in real-time:

• provides evidence for single introduction into Bulgaria from Turkey • long branches indicative of unsampled infection • either in 4 villages with seropositive domesticated animals • or wildlife (wild boar) BUL/1/2010

12LPN1 Closest Turkish 12LPN3 virus BUL/11/2011

BUL/30/2011 BUL/26/2011 TCS tree showing linking samples showing putative unsampled BUL/20/2011 intermediates (-O-) BUL/32/2011

Valdazo-Gonzalez et al., PLoS ONE (2012) Sub-consensus changes: C1 C2 C3 C4

Transmission direction

Lost

Drifting

Fixed

Wright et al., 2011 J. Virol. ; Morelli et al., 2013 Vet Res. FMDV evolution at different scales Global Phylogeography

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farm-to-farm Data can be used to: spread

animal-animal • Monitor the global circulation transmission and transboundary movements within host of FMDV pathways

cell-to-cell • reconstruct transmission trees infection

within outbreaks X X X X X X X Population X X X X X X X diversity X X X X X X • reveal processes that drive intra-cellular dynamics evolution 5’ AAAA Orton et al., Phil Trans B (2013) Tools for FMD Control

Success of reactive strategies, such as quarantines and culling, depend upon how long animals infectious before confirm disease, usually based on clinical signs

Proxy measures used based on viraemia/virus excretion

Black – transmission attempt outcome Green – virus isolation from nasopharynx Red – virus isolation from blood Blue – virus isolation from probang

Charleston et al., Science (2011) External partnerships

• Diamond Light Source synchrotron • Located in South Oxfordshire on the Harwell Science and Innovation Campus. • Covers the area of 5 football pitches

• Recent approval to use beamlines for FMDV

• Provides capability to define viral capsid structures at high resolution FMD Capsid vaccines – safe and stable

Stabilised capsids treated 2h at 56ºC (or for 30min at pH5) are intact after sucrose density gradient analysis

Porta et al., PLoS Pathog (2013) National capability facilities

• CL3/4 biocontainment laboratories, large & small animal facilities (Pirbright) • CL2 biocontainment laboratories, & small animal /avian facilities (Compton) • Insectary (CL2/3) (Pirbright) • Inbred animal lines, arbovirus vector colonies, virus collections Large animal isolation facilities

24 rooms: each can have 4 or 5 cattle, 12 pigs or 8 sheep (depending on age/size) Campus redevelopment

The Institute’s main campus is undergoing a renaissance • Laboratories at various levels of containment thanks to significant financial • Animal facilities investment from the UK • Commercial zone government via the • Accommodation Biotechnology and • Conference centre Biological Sciences • Social facilities Research Council. Planned new facilities include:

Phase 1: DP1 building Phase 1: DP1 building Phase 1: DP1 building

• SAPO4 high containment envelope • To be completed in 2014 • Commissioned 2015/16 • £130m

Phase 1: DP1 building Phase 1: DP1 building Phase 1: DP1 building Phase 1: DP1 building Phase 2: CL2 building

• Containment Level 2 Laboratory • Work to start in 2013 • Commissioned 2015 • Part of DP phase 2 (£100m) Phase 2: CL2 building

FUTURE: 2020 and beyond

PROPOSED SITE MASTERPLAN

Funding

Industrial - UK only, 4,464 International (non- EU), 477,853 Trusts / Foundations / Commercial Income, Charities / Other - UK 3,933,000 only, 514,109 EU Grant Funding, BBSRC Core Grant, 1,312,137 11,119,000 DEFRA Surveillance, 1,963,500

DEFRA , 4,153,922

BBSRC Grants, 4,903,269 A national capability

The Pirbright Institute has a unique combination of

• Expertise • High bio-containment laboratories and animal facilities • Exclusive biological resources • Extensive reference virus collections • Arthropod vector colonies • Genetically defined farm animal host species • Diagnostic services

Our science

Specialist fields at the Institute include:

• Bioimaging • Immunology • Bioinformatics • Mathematical biology • Diagnostics • Molecular and Structural biology • Entomology • Pathology • Epidemiology • Proteomics • Genetics • Vaccinology • Genomics • Virology

Japan 2010 • 292 infected farms (Apr-Jul) • 298,000 animals culled • 1,011 farms vaccinated • Cull indemnity €440m

Korea 2010-11 • Three incursions (2 serotypes) • 3.3m pigs and 150,000 cattle culled • 8.3m pigs and 3.5m cattle vaccinated • Total costs run to $billions

Bulgaria 2011 • Wild boar near Turkish Thrace

Pen-side diagnostics

SVANODIP® FMDV-Ag Mesosystems: non-invasive air samplers

Portable molecular assays: Genie III for Infra-red thermography LAMP and Enigma diagnostics for PCR Phase 2: BRF building ACDP4 Laboratory Layout Elec./ Data Outlet (typ).

D

D

Decon/Neut. HCW CO2 Outlet

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Animal watering D lines @ 1800mm CO2 aff

Vision panel with light control device; Rapid transfer port below Phase 2: BRF building Our science

Current diseases of interest are:

• Nairobi sheep disease • African Horse sickness • Peste des petits ruminants • African swine fever • Pestiviruses • Avian influenza • Bovine and human respiratory syncytial • Bluetongue viruses • Foot-and-mouth diseases • Rotaviruses • Infectious bronchitis • Schmallenberg • Infectious bursal disease • Swine influenza • Marek’s disease • Zoonotic arboviruses Social and economic impact

The Pirbright Institute provides knowledge, tools, technologies and advice to a variety of end users in science, , , pharmaceutical industries and policy. Activities include:

• Diagnostic Services and Surveillance • Knowledge Exchange and Commercialisation • International Training • Health and Safety, Environmental Protection, Biosecurity, and Risk Management • Public Engagement Social and economic impact

Fundamental science underpins practical solutions to many of the challenges faced by farmers, vets and policy makers. The benefits can be world-changing:

• The Institute has played a role in eradicating rinderpest, which is estimated to save the economies of Africa around US$1 billion per year.

• Advice from the Institute led to a successful voluntary vaccination programme against an incursion of bluetongue virus in 2007-8, saving the UK around £485 million and protecting 10,000 jobs.