Pirbright Instituteiiad.tamu.edu/wp-content/uploads/2013/07/King.pdfThe Pirbright Institute is a...
Transcript of Pirbright Instituteiiad.tamu.edu/wp-content/uploads/2013/07/King.pdfThe Pirbright Institute is a...
Pirbright Institute Preventing and controlling viral diseases
Don King [email protected]
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
About us
(Poultry data provided by Peter Bradnock (CEO, British Poultry Council) & Mark Williams (CEO, British Egg Industry Council)
Cattle£4,487M
Sheep £628M
Horses£4,000M
Pigs£735M
Poultry£7,500M
Game£1,600M
Annual contribution of livestock to the UK economy
Impact: UK economy
• Foot-and-mouth outbreak 2001 cost UK economy >£2-8bn
• Calf pneumonia costs UK economy £54m p.a.
• IBV costs UK economy £22m p.a.
• Prediction and rapid response to bluetongue in 2007 saved economy £0.5bn p.a.
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.
LVD SIV
PPRV
CSFV FMDV
BRSV
BVDV
VVD NSDV EEV
RVFV
ASFV
AHSV
BTV
WNV
AVD ALV-J
IBV
ILTV
AIV
IBDV
MDV
FPV
Institute Strategic Programmes
RPV
Virus biology, gene functions, evolution
Virus-host interactions in
infection models in natural hosts
Immune responses to
virus infections & vaccines
Interactions between disciplines
Role of arthropod vectors in virus transmission
Diagnostics, disease surveillance, mathematical
modelling
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
• Tracing sources of outbreaks • Vaccine selection
What we do…..
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East Asia incursions: 2010-2011 (O/SEA/Mya-98)
O/CHA/109/2010* (LVRI)
O/CHA/84/2010* (LVRI)
O/CHA/114/2010* (LVRI)
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
O/HKN/7/2010
O/CHA/51/2010* (LVRI)
O/SKR/4/2010
O/CHA/106/2010* (LVRI)
O/CHA/104/2010* (LVRI)
O/CHA/72/2010* (LVRI)
O/CHA/39/2010* (LVRI)
O/HKN/19/2010
O/CHA/64/2010* (LVRI)
O/HKN/6/2010
O/HKN/1/2010
O/CHA/107/2010* (LVRI)
O/CHA/82/2010* (LVRI)
O/CHA/80/2010* (LVRI)
O/TAI/22/2009 (HQ116269)
O/MYA/5/2009 (HQ116228)
O/MYA/11/2009 (HQ116232)
O/MYA/3/2010
O/MOG/2004 (ARRIAH)
O/HLJOC12/03 (China) (DQ119643)
O/MYA/1/2006
O/MYA/3/2009
O/MYA/2/2006 (HQ116225)
O/VIT/5/2010
O/TAI/20/2009 (HQ116267)
O/MYA/12/2009
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)
O/TAI/6/2008 (HQ116253)
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)
O/TAI/13/2009 (HQ116261)
O/TAI/12/2009 (HQ116260)
O/MOG/66/2010* (ARRIAH)
O/MOG/9/2010
O/MOG/6/2010
O/MOG/77/2010* (ARRIAH)
O/MOG/7/2010
O/MOG/5/2010
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
O/TAI/189/87* (TRRL)
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Tracking spread of FMDV
Complete FMDV sequences can resolve farm-to-farm spread
Valdazo-Gonzalez et al., PLoS ONE (2012)
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
12LPN3
12LPN1
BUL/11/2011
BUL/26/2011BUL/30/2011
BUL/32/2011
BUL/20/2011
Closest Turkish
virus
TCS tree showing linking samples showing putative unsampled intermediates (-O-)
Sub-consensus changes: C3 C1 C2
Transmission direction
C4
Lost
Drifting
Fixed
Wright et al., 2011 J. Virol. ; Morelli et al., 2013 Vet Res.
Global Phylogeography
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intra-cellular dynamics
Population diversity
animal-animal transmission
farm-to-farm spread
Outbreak epidemiology
cell-to-cell infection
within host pathways
X X XX XX XX XX XX XXX XX X XX
5’ AAAA
FMDV evolution at different scales
Orton et al., Phil Trans B (2013)
• Sequence data for FMDV (VP1 ► complete genome ► deep-seq)
Data can be used to:
• Monitor the global circulation
and transboundary movements of FMDV
• reconstruct transmission trees within outbreaks
• reveal processes that drive evolution
Charleston et al., Science (2011)
Success of reactive strategies, such as quarantines and culling, depend upon how long animals infectious before confirm disease, usually based on clinical signs
Black – transmission attempt outcome Green – virus isolation from nasopharynx Red – virus isolation from blood Blue – virus isolation from probang
Proxy measures used based on viraemia/virus excretion
Tools for FMD Control
• 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
External partnerships
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
24 rooms: each can have 4 or 5 cattle, 12 pigs or 8 sheep (depending on age/size)
Large animal isolation facilities
The Institute’s main campus is undergoing a renaissance thanks to significant financial investment from the UK government via the Biotechnology and Biological Sciences Research Council. Planned new facilities include:
• Laboratories at various levels of
containment • Animal facilities • Commercial zone • Accommodation • Conference centre • Social facilities
Campus redevelopment
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
BBSRC Core Grant, 11,119,000
BBSRC Grants, 4,903,269
DEFRA , 4,153,922
DEFRA Surveillance, 1,963,500
EU Grant Funding,
1,312,137
Trusts / Foundations / Charities / Other - UK
only, 514,109
International (non-EU), 477,853
Industrial - UK only, 4,464
Commercial Income, 3,933,000
Funding
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
A national capability
Specialist fields at the Institute include:
• Bioimaging • Bioinformatics • Diagnostics • Entomology • Epidemiology • Genetics • Genomics
• Immunology • Mathematical biology • Molecular and Structural biology • Pathology • Proteomics • Vaccinology • Virology
Our science
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
Mesosystems: non-invasive air samplers
Infra-red thermography
SVANODIP® FMDV-Ag
Portable molecular assays: Genie III for LAMP and Enigma diagnostics for PCR
ACDP4 Laboratory Layout
Vision panel with light control device; Rapid transfer port below
HCW
Animal watering lines @ 1800mm aff CO2
D
Decon/Neut. Outlet
Elec./ Data Outlet (typ). D
D
CO2
D
Phase 2: BRF building
Phase 2: BRF building
Current diseases of interest are:
• African Horse sickness • African swine fever • Avian influenza • Bluetongue • Foot-and-mouth diseases • Infectious bronchitis • Infectious bursal disease • Marek’s disease
• Nairobi sheep disease • Peste des petits ruminants • Pestiviruses • Bovine and human respiratory syncytial
viruses • Rotaviruses • Schmallenberg • Swine influenza • Zoonotic arboviruses
Our science
Social and economic impact
The Pirbright Institute provides knowledge, tools, technologies and advice to a variety of end users in science, agriculture, veterinary medicine, 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
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.
Social and economic impact