Update from WRLFMD Donald King

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1 Update from WRLFMD Donald King 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 FMD Reference Laboratory

2 OIE/FAO FMD Laboratory Network Global surveillance and changing patterns in risk Harmonised and improved lab capacity Working Groups for: Virus nomenclature Vaccines (selection and PVM) Core Network Members and affiliates: MoU now signed by 14/15 of the core members Thanks to and Meeting report available: Pretoria November 2017

3 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) Pool 1 Pool 2 Pool 3 Pool 4 Pool 5 Pool 6 Pool 7 *preliminary data for 2017

4 Recent submissions to WRLFMD Pirbright Q 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 Submissions:

5 FMD situation highlights Algeria/Tunisia Serotype A Russia/Pakistan Serotype O Nepal Serotypes O/Asia 1 East Asia Serotype O Colombia Serotype O Near East Serotype O/A/SAT 2 Myanmar Serotype Asia 1

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

7 O/ME-SA lineage in Russia October 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?

8 Poor ag-match for serotype O viruses from Pakistan Two isolates in a new genetic clade within O/ME-SA/PanAsia-2 ANT-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

9 Preliminary analyses: Vaccine matching O 3039 O Manisa O TUR/5/2009 O/PAK/14/ O/PAK/10/ O/PAK/4/ VP1 O/PAK/14/2017 O/PAK/10/2016 O/PAK/4/2017 O/PAK/14/2017 O/PAK/10/2016 O/PAK/4/2017 O/PAK/14/2017 O/PAK/10/2016 O/PAK/4/ Ag site 3 TTSAGESSDPVTATVENYGGETQVQRRQHTDVSFILDRFVKVTPKDQINVLDLMQTPAHTLVGALLRTATYYFADLEVAV...A...T......A Ag site 1 KHEGNLTWVPNGAPEAALDNTTNPTAYHKAPLTRLALPYTAPHRVLATVYNGNCKYGESHVPNVRGDLQVLAQKAARALP...D...T...T......D...T...S...T...T Ag site 1 TSFNYGAIKATRVTELLYRMKRAETYCPRPLLAIHPDAARHKQKIVAPVKQLL...V..NE......NE... Known type O antigenically important residues are underlined Residue 198 has been shown to be part of site 1 in type A viruses Complete genome sequences will also be determined using the Illumina MiSeq

10 Molecular clocks Are these a predictable indicator of FMDV replication in hosts? FMDV genome (Error rate replication event) Genome replication Genome replication Genome replication Genome replication Genome replication Etc.

11 Analyses of samples from Nepal Highlights 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 change 2. Un-sampled cases

12 2017/18 FMD situation highlights Algeria/Tunisia Serotype A Russia/Pakistan Serotype O Nepal Serotypes O/Asia 1 East Asia Serotype O Colombia Serotype O Near East Serotype O/A/SAT 2 Myanmar Serotype Asia 1

13 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 Cruzeiro Asia 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 Eritrea SAT 2 Zimbabwe SAT 1 South Africa A Malaysia 97 (or Thai equivalent such as A/Sakolnakorn/97) A Argentina 2001 O Taiwan 97 (pig-adapted strain or Philippine equivalent) Low Priority A Iran 96 A Iran 99 A Iran 87 or A Saudi Arabia 23/86 (or equivalent) A15 Bangkok related strain A87 Argentina related strain C Noville SAT 2 Kenya SAT 1 Kenya SAT 3 Zimbabwe

14 A new tool for vaccine antigen selection WRLFMD/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 components 1. 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

15 Estimating risks for Europe Likely source of FMDV FMDV lineages that are present in source regions

16 Vaccine Antigen Prioritisation: Europe March 2018 Regional risks: DEFINING RISK Risk Profile: SELECTING VACCINES 40% 0% Viral lineages: A/ASIA/G-VII O/ME-SA/Ind2001 Vaccine Coverage: 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] 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] Asia1-Shamir [HIGH] SAT-1 Rho/78 [MEDIUM] SAT2 Eritrea 3218 [HIGH] SAT2-ZIM [MEDIUM] Insufficient Data: C3 Oberbayern [LOW]; SAT2 SAU [HIGH]; SAT3 ZIM 2/83 [LOW] NB: Analyses uses best available data, however there are gaps in surveillance and vaccine coverage data

17 Update on the proficiency testing scheme To assist NRLs to employ accurate and reproducible FMD diagnostic tests Quality assurance programme requirements at ISO/IEC PT panel(s) have been sent to 24 countries: Albania, Algeria, Armenia, Azerbaijan, Botswana (shipping 2 nd March), Brazil, Ethiopia, Georgia, Israel, Kenya, Kosovo, Lebanon, Macedonia, Moldova, Morocco, Nigeria, Norway, Russia, Senegal, Serbia, South Africa, Switzerland, Thailand (shipping 2 nd 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 2018 BOLD countries Global Network

18 East Africa Laboratory 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

19 Observations regarding FMDV vaccines Particularly 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 crossprotective 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

20 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) Network Ref Labs National Ref Labs CVO (policy) Vaccine Producers Customer Farmer Vaccine Producers Goals of vaccination need to be agreed (control vs eradication in zones vs trade benefits)

21 2018: some important dates May 8-9: EU Workshop Horsley, UK May 14-25: FMD Diagnostics training course Pirbright November 5-6: Symposium to celebrate 60 th Anniversary of WRLFMD 50 th Anniversary 2008 Royal Society, London, 2008

22 Acknowledgements Support for the WRLFMD and research projects Collaborating FMD Reference Laboratories and field teams Partners within the OIE/FAO FMD Lab Network

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