Pirbright Institute Preventing and controlling viral diseases. Don King
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1 Pirbright Institute Preventing and controlling viral diseases Don King
2 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
3 Impact: UK economy Annual contribution of livestock to the UK economy Poultry 7,500M Game 1,600M Pigs 735M Cattle 4,487M Horses 4,000M Sheep 628M 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. (Poultry data provided by Peter Bradnock (CEO, British Poultry Council) & Mark Williams (CEO, British Egg Industry Council)
4 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.
5 Institute Strategic Programmes CSFV FMDV RPV LVD BVDV SIV PPRV RVFV ASFV BTV BRSV ILTV AIV MDV NSDV VVD EEV ALV-J AVD IBV WNV AHSV FPV IBDV
6 Interactions between disciplines Diagnostics, disease surveillance, mathematical modelling Immune responses to virus infections & vaccines Virus biology, gene functions, evolution Virus-host interactions in infection models in natural hosts Role of arthropod vectors in virus transmission
7 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
8 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
9 Translating basic science into tools for disease control: Foot-and-mouth disease (FMD)
10 FMD is a global problem The conjectured status of FMD showing principal virus pools
11 What we do.. Tracing sources of outbreaks Vaccine selection
12 Tracking spread of FMDV O/CHA/109/2010* (LVRI) O/CHA/84/2010* (LVRI) O/CHA/114/2010* (LVRI) O/CHA/117/2010* (LVRI) 2 81 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/ O/CHA/106/2010* (LVRI) 75 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/ O/HKN/1/ 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/ O/MOG/2004 (ARRIAH) 98 O/HLJOC12/03 (China) (DQ119643) O/MYA/1/ O/MYA/3/2009 O/MYA/2/2006 (HQ116225) O/VIT/5/2010 O/TAI/20/2009 (HQ116267) O/MYA/12/ O/MYA/3/2008 (HQ116227) 2 3 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) 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/ O/MOG/CO3/2010* (ARRIAH) O/RUS/Aug 2010 (ARRIAH) East Asia incursions: (O/SEA/Mya-98) O/TAI/189/87* (TRRL) O/MOG/2/2010 O/MOG/1/2010 O/MOG/56/2010* (ARRIAH) O/MOG/4/2010 O/MOG/3/2010
13 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 Closest Turkish virus 12LPN1 12LPN3 BUL/11/2011 TCS tree showing linking samples showing putative unsampled intermediates (-O-) BUL/30/2011 BUL/26/2011 BUL/20/2011 BUL/32/2011 Valdazo-Gonzalez et al., PLoS ONE (2012)
14 Sub-consensus changes: C1 C2 C3 C4 Transmission direction Lost Drifting Fixed Wright et al., 2011 J. Virol. ; Morelli et al., 2013 Vet Res.
15 ( FMDV evolution at different scales Global Phylogeography Sequence data for FMDV (VP1 complete genome deep-seq) Outbreak epidemiology Data can be used to: farm-to-farm spread Monitor the global circulation and transboundary movements of FMDV animal-animal transmission within host pathways reconstruct transmission trees within outbreaks reveal processes that drive evolution Orton et al., Phil Trans B (2013) X X X X X X X X X X X X X X X X X X X X 5 AAAA cell-to-cell infection Population diversity intra-cellular dynamics
16 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)
17 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 External partnerships Provides capability to define viral capsid structures at high resolution
18 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)
19 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
20 Large animal isolation facilities 24 rooms: each can have 4 or 5 cattle, 12 pigs or 8 sheep (depending on age/size)
21 Campus redevelopment 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
22 Phase 1: DP1 building
23 Phase 1: DP1 building
24 Phase 1: DP1 building SAPO4 high containment envelope To be completed in 2014 Commissioned 2015/16 130m
25 Phase 1: DP1 building
26 Phase 1: DP1 building
27 Phase 1: DP1 building
28 Phase 1: DP1 building
29 Phase 2: CL2 building Containment Level 2 Laboratory Work to start in 2013 Commissioned 2015 Part of DP phase 2 ( 100m)
30 Phase 2: CL2 building
31
32 PROPOSED SITE MASTERPLAN FUTURE: 2020 and beyond
33
34 Funding Industrial - UK only, 4,464 International (non- EU), 477,853 Trusts / Foundations / Charities / Other - UK only, 514,109 EU Grant Funding, 1,312,137 DEFRA Surveillance, 1,963,500 Commercial Income, 3,933,000 BBSRC Core Grant, 11,119,000 DEFRA, 4,153,922 BBSRC Grants, 4,903,269
35 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
36 Our science Specialist fields at the Institute include: Bioimaging Bioinformatics Diagnostics Entomology Epidemiology Genetics Genomics Immunology Mathematical biology Molecular and Structural biology Pathology Proteomics Vaccinology Virology
37 Japan infected farms (Apr-Jul) 298,000 animals culled 1,011 farms vaccinated Cull indemnity 440m Korea 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
38 Pen-side diagnostics SVANODIP FMDV-Ag Mesosystems: non-invasive air samplers Portable molecular assays: Genie III for LAMP and Enigma diagnostics for PCR Infra-red thermography
39 ACDP4 Laboratory Layout Phase 2: BRF building D Elec./ Data Outlet (typ). D Decon/Neut. Outlet HCW CO2 D Animal watering 1800mm aff D CO2 Vision panel with light control device; Rapid transfer port below
40 Phase 2: BRF building
41 Our science 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
42 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
43 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 , saving the UK around 485 million and protecting 10,000 jobs.
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