FMD Reference Laboratory

Update from WRLFMDDonald King

donald.king@pirbright.ac.uk

WRLFMD Team: Valerie Mioulet, Nick Knowles, Anna Ludi, Ginette Wilsden, Mehreen Azhar, Hannah Baker, Kasia Bachanek-Bankowska, Lissie Henry,

Antonello Di Nardo, Jemma Wadsworth, Clare Browning, Britta Wood, Bob Statham, Abid Bin-Tarif, Ashley Gray, Beth Johns, Mark Henstock,

Alison Morris, David Paton, Nick Lyons, Dexter Wiseman, Julie Maryan, Sarah Belgrave

• Global surveillance and changing patterns in risk

• Harmonised and improved lab capacity

• Working Groups for:• Virus nomenclature• Vaccines (selection and PVM)

• MoU now signed by 14/15 of the “core members”

• Thanks to and

• Meeting report available: http://www.foot-and-mouth.org/

Pretoria– November 2017

Core Network Members and affiliates:

OIE/FAO FMD Laboratory Network

Global surveillance via the OIE/FAO FMD Laboratory Network

• Since 2014 >2000 virological samples pa• Results collated in Annual Report (2017 in draft form)• Review geographical distribution of transboundary FMDV

lineages • new way to highlight risks

• Gaps in surveillance remain in West/Central (and East Africa)

*preliminary data for 2017

269

242

544

335

19

389

2

Pool 1 Pool 2 Pool 3 Pool 4 Pool 5 Pool 6 Pool 7

Q4 2017 to date:

Reports issued for:Afghanistan, Botswana, Bhutan, China*, Egypt (and*), Ghana, Hong Kong SAR, Israel, Kenya, Malawi, Mongolia*, Myanmar*, Namibia, Nepal, Pakistan, Palestine, Russia*, Sri Lanka, Tunisia*, Turkey*, Uganda, Zambia, Zimbabwe (23 countries – including sequence exchange*)

Results pending for:Vietnam

Arranging shipments:Ethiopia, Iran, Swaziland

Recent submissions to WRLFMD Pirbright

Submissions:

FMD situation – ”highlights”

ColombiaSerotype O

East AsiaSerotype O

MyanmarSerotype Asia 1

Algeria/TunisiaSerotype A

Near EastSerotype O/A/SAT 2

Russia/PakistanSerotype O

NepalSerotypes O/Asia 1

• Sequences from NIAH/NARO, Japan (from Genbank)

• Samples collected in March, 2015 from Bayan-Ulgii (western-most Aimag of Mongolia)

• 99.4% identity to sequences from FGBI-ARRIAH (collected in Eastern Mongolia in 2017) – reported in Dublin

• Pre-dates reports of this lineage in China and Russia – similar dates to first reports of this lineage in mainland SEA

O/ME-SA/Ind-2001Evidence that this lineage has been in Mongolia for > 2 years

• 5 FMD outbreaks reported in Bashkortostan (in the FMD-free zone without vaccination)

• Reported cases in cattle, sheep and goats

• New FMDV lineage in ME-SA topotype(not PanAsia or PanAsia-2)

• Most closely related to FMD viruses in Pakistan and Iran (2014)

• Reporting of cases in “central Asia”?

O/ME-SA lineage in RussiaOctober 2017

• Two isolates in a new genetic clade within O/ME-SA/PanAsia-2ANT-10

• Discrete from other ANT-10 viruses• Collected in Punjab, Pakistan

(2016/17) from cattle and water buffalo

• No neutralization in VNT with BVS for O-Manisa, O-3039 or O-TUR-5-09

• New antigenic variant?• Spread of this lineage needs to be

closely monitored – esp. wrt evidence of vaccine failure in the field

Poor ag-match for serotype O viruses from Pakistan

10 20 30 40 50 60 70 80....|....|....|....|....|....|....|....|....|....|....|....|....|....|....|....|

Ag site 3O/PAK/14/2017 TTSAGESSDPVTATVENYGGETQVQRRQHTDVSFILDRFVKVTPKDQINVLDLMQTPAHTLVGALLRTATYYFADLEVAVO/PAK/10/2016 .......A....T...................................................................O/PAK/4/2017 .......A........................................................................

90 100 110 120 130 140 150 160 ....|....|....|....|....|....|....|....|....|....|....|....|....|....|....|....|

Ag site 1O/PAK/14/2017 KHEGNLTWVPNGAPEAALDNTTNPTAYHKAPLTRLALPYTAPHRVLATVYNGNCKYGESHVPNVRGDLQVLAQKAARALPO/PAK/10/2016 ....D..........T.............................................T..................O/PAK/4/2017 ....D..........T........................................S....T...............T..

170 180 190 200 210 ....|....|....|....|....|....|....|....|....|....|...

Ag site 1O/PAK/14/2017 TSFNYGAIKATRVTELLYRMKRAETYCPRPLLAIHPDAARHKQKIVAPVKQLLO/PAK/10/2016 .................................V..NE...............O/PAK/4/2017 ....................................NE...............

• VP1

• Complete genome sequences will also be determined using the Illumina MiSeq

Known type O antigenically important

residues are underlined

Vaccine matching O 3039 O Manisa O TUR/5/2009

O/PAK/14/2017 0.62 0.32 0.48

O/PAK/10/2016 0 0 0

O/PAK/4/2017 0 0.10 0

Residue 198 has been shown to be part of site 1 in type A viruses

↑

Preliminary analyses:

Genomereplication

Genomereplication

Genomereplication

Genomereplication

Genomereplication

X

X

X

X

X

X

X

X

X

X

X

X

X

XX

Etc….

FMDV genome

Molecular clocks

(Error rate 10-2-10-4 replication event)

Are these a predictable indicator of FMDV replication in hosts?

Analyses of samples from NepalHighlights gaps in regional/National surveillance?

Serotype O:~94% identity with closest sequences

Serotype Asia 1:~91% identity with closest sequences

How do we interpret these trees?1. Rapid evolutionary

change2. Un-sampled cases

2017/18 FMD situation – ”highlights”

ColombiaSerotype O

East AsiaSerotype O

MyanmarSerotype Asia 1

Algeria/TunisiaSerotype A

Near EastSerotype O/A/SAT 2

Russia/PakistanSerotype O

NepalSerotypes O/Asia 1

Vaccine Bank Recommendations (October 2017)

High Priority

A/ASIA/G-VII(G-18)*O Manisa

O PanAsia-2 (or equivalent)O BFS or Campos

A24 CruzeiroAsia 1 Shamir

A Iran-05 (or A TUR 06)A22 Iraq

SAT 2 Saudi Arabia (or equivalent i.e. SAT 2 Eritrea)

Medium Priority

A EritreaSAT 2 Zimbabwe

SAT 1 South AfricaA Malaysia 97 (or Thai equivalent such as A/Sakolnakorn/97)

A Argentina 2001O Taiwan 97 (pig-adapted strain or Philippine equivalent)

Low Priority

A Iran ‘96A Iran ‘99

A Iran 87 or A Saudi Arabia 23/86 (or equivalent)A15 Bangkok related strainA87 Argentina related strain

C NovilleSAT 2 KenyaSAT 1 Kenya

SAT 3 Zimbabwe

A new tool for vaccine antigen selectionWRLFMD/EuFMD

• Improved (more transparent) categorisation of different FMDV vaccine antigens

• Ability to respond to changing epidemiological risks• Accommodates use of vaccines across different lineages • For use in FMD-free settings• Data can be challenged/modified (Excel format)

Determines scores as a product of two components1. Different risks and associated FMDV lineages the are

specific to a particular region (Europe, NA, Aus/NZ)2. Uses available in-vitro, in-vivo and field data to score the

ability of available vaccines to protect against the different lineages

Estimating risks for Europe

Likely source of FMDV

FMDV lineages that are present in ”source” regions

Vaccine Antigen Prioritisation: Europe

SELECTING VACCINES

March 2018

NB: Analyses uses best available data, however there are gaps in surveillance and vaccine coverage data

Insufficient Data: C3 Oberbayern [LOW];SAT2 SAU [HIGH];SAT3 ZIM 2/83 [LOW]

Risk Profile:

O-TUR/5/2009 [HIGH]O-3039 [HIGH]O1-Manisa [HIGH]O1-Campos [HIGH]O-BFS/1860 [LOW]O-SKR/7/2010 [LOW]O-TAW/98 [↓ LOW]

A-TUR/2006 [HIGH]A22 Iraq [HIGH]

A-Iran-05 [HIGH]A-Malaysia 97 [↑ HIGH]

A-Eritrea [MEDIUM]A-SAU 95 [LOW]

A24 Cruzeiro [↓LOW]Asia1-Shamir [HIGH]

SAT2 Eritrea 3218 [HIGH]SAT2-ZIM [MEDIUM]

SAT-1 Rho/78 [MEDIUM]

Vaccine Coverage:

DEFINING RISK

O/ME-SA/Ind2001A/ASIA/G-VII

40%

0%

Regional risks:

Viral lineages:

Update on the proficiency testing scheme• To assist NRLs to employ accurate and reproducible FMD

diagnostic tests• Quality assurance programme requirements at ISO/IEC 17025• 2017 PT panel(s) have been sent to 24 countries: Albania,

Algeria, Armenia, Azerbaijan, Botswana (shipping 2nd March), Brazil, Ethiopia, Georgia, Israel, Kenya, Kosovo, Lebanon, Macedonia, Moldova, Morocco, Nigeria, Norway, Russia, Senegal, Serbia, South Africa, Switzerland, Thailand (shipping 2nd March), Turkey

• Awaiting export licences for: Argentina, Egypt, Iraq and Tunisia• Following labs have been contacted but no response: Belarus,

Bosnia & Herzegovina, India, Iran, Libya, Syria.• Ukraine confirmed they were unable to participate and Republic

of Korea, China and Montenegro would like to take part in 2018BOLD countries – Global Network

• Regional meeting of EALN-FMD (December 2017)

Aims:• Share information about the FMD situation in the region• Review FMD laboratory diagnostic capacity in East Africa• Decide on immediate training priorities for lab diagnostics• Develop and encourage a more sustainable Network platform

for regional FMD lab activities

East Africa Laboratory Network

Observations regarding FMDV vaccinesParticularly for Africa (from OIE/FAO and EALN-FMD Network Meetings)

There are many gaps in our knowledge:[1] in vivo potency tests are rarely done,

particularly those that define cross-protective responses

[2] Immunogenicity studies for monovalent (or multivalent vaccines) are rarely reported

[3] Reference reagents (such as validated BVS) from vaccines suppliers are not readily available to the Reference laboratory community

[4] not clear that batch serological testing data is always supplied from manufacturers in Africa

[5] Field evaluation studies are lacking

Priorities for FMDV vaccine quality assurance • Defining key roles for the different

“actors” • Laboratory support to generate

independent evidence regarding the suitability of vaccines in different endemic settings

• Generation/validation of tailored tools

• Developing capacity/expertise for these activities for international and local producers

• Scope to enhance these activities via proposed OIE Twinning Project (with PANVAC)

National Ref Labs

NetworkRef Labs

Customer

Farmer

VaccineProducers

VaccineProducers

CVO (policy)

Goals of vaccination need to be agreed (control vs eradication in zones vs trade benefits)

2018: some important dates

50th Anniversary2008

Royal Society, London, 2008

• May 8-9: EU Workshop – Horsley, UK• May 14-25: FMD Diagnostics training course – Pirbright• November 5-6: Symposium to celebrate 60th Anniversary of

WRLFMD

Acknowledgements

• Support for the WRLFMD and research projects

• Collaborating FMD Reference Laboratories and field teams

• Partners within the OIE/FAO FMD Lab Network