Pirbright Instituteiiad.tamu.edu/wp-content/uploads/2013/07/King.pdfThe Pirbright Institute is a...

Pirbright Institute Preventing and controlling viral diseases

Don King donald.king@pirbright.ac.uk

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

CSFV FMDV

VVD NSDV EEV

AVD ALV-J

Institute Strategic Programmes

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

• 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…..

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/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/4/2010

O/MOG/3/2010

O/TAI/189/87* (TRRL)

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

TCS tree showing linking samples showing putative unsampled intermediates (-O-)

Sub-consensus changes: C3 C1 C2

Transmission direction

Drifting

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 • SAPO4 high containment

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

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

Animal watering lines @ 1800mm aff CO2

Decon/Neut. Outlet

Elec./ Data Outlet (typ). D

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

Pirbright Instituteiiad.tamu.edu/wp-content/uploads/2013/07/King.pdfThe Pirbright Institute is a...

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