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VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH-EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ; Bowden, Timothy 1 ; Thongtha, Panithan 2 ; Samanit, Janya 2 ; Kamolsiripichaiporn, Somjai 2 & Vosloo, Wilna 1 1 CSIRO Australian Animal Health Laboratory, Private Bag 24, Geelong, Victoria 3220, Australia 2 OIE-Regional Reference Laboratory for FMD in SEA, Pakchong, Nakhonratchasima 30130, Thailand CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY GFRA 2015, Hanoi, Vietnam; September 22, 2015

VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

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Page 1: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV

SEROTYPE O AND A ISOLATES IN SOUTH-EAST ASIA

Singanallur, Nagendrakumar1; Seeyo, Kingkarn2; Bowden, Timothy1; Thongtha, Panithan2; Samanit, Janya2; Kamolsiripichaiporn, Somjai2 & Vosloo, Wilna1

1CSIRO Australian Animal Health Laboratory, Private Bag 24, Geelong, Victoria 3220, Australia2OIE-Regional Reference Laboratory for FMD in SEA, Pakchong, Nakhonratchasima 30130, Thailand

• CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

GFRA 2015, Hanoi, Vietnam; September 22, 2015

Page 2: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

FMD & Australia• Minor outbreaks of possible FMD:

1801, 1804, 1871 and 1872• Pre- and post border controls are essential• Up-to-date vaccine/antigen bank ?

Disease hotspots

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 3: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

FMD in South East Asia

• FMD is endemic in most SEA countries with the exception of• Philippines, Indonesia, Malaysia (Sarawak/Sabah regions) and Singapore

• Major direct impact on livelihoods of farmers and impediment for access to international markets

• Factors driving epidemics are not always clear• poor quality vaccines, inability to perform blanket vaccination, extensive

transboundary animal movement and lack of financial support for effective control programs in different countries

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 4: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

AAHL’s activities in SEA• AAHL through its overseas program actively engages with member

countries in the SEA with support from OIE and FAO

• FMD-RMP’s aim is to collaborate with RRL, Pakchong in the area of vaccine matching and take part in studying the epidemiology of the disease

• Most of the countries in the region, except Thailand, use commercial vaccines that are also present in antigen banks

• It is therefore essential to compare the field isolates with the vaccine strains in the vaccine banks along with the vaccine strains used in Thailand

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 5: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

• Bovine vaccinate serum• O1 Manisa• O TAI/187/87 Udorn Thani (Thai vaccine strain)

• A22 Iraq 64• A MAY 97• A TAI/2012 Lopburi (Thai vaccine strain)

• Homologous reagents

• Field isolates from Thailand, Lao PDR, Vietnam, Cambodia

Antigen matching studies in collaboration with RRL Pakchong - LPBE

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 6: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

Antigenic relationship of SEA isolates with O1 Manisa

O LAO 13/12 O TAI 30/13O TAI 28/13 O TAI 94/1/14

O LAO 11/12 O TAI 36/13 O TAI 42-2/14O TAI 125/14 O TAI 164/14 O TAI 19/15

O LAO 10/12 O LAO 19/12 O LAO 21/12 O CAM 1/12O CAM 4/12 O LAO 18/12 O LAO 14/12 O LAO 20/12O TAI 29/12 O TAI 2/13 O TAI 27/13 O TAI 33/13O TAI 38/13 O TAI 44/13 O TAI 51/13 O TAI 35/13O TAI 42/3/14 O TAI 69/1/14 O TAI 123/1/14 O TAI 145/14O TAI 154/14 O TAI 148/2/14 O TAI 49/1/14 O TAI 146/14

O TAI 10/1/15 O TAI 11/2015 O TAI 13/1/15 O TAI 15/1/15 O TAI 17/15 O LAO 2/15 O LAO 3/15

Homologous(Good Match)

Intermediary(Poor Match)

Heterologous(No Match)

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 7: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

<0.2 – Heterologous; 0.2-0.39 – Intermediary; >0.39 – Homologous (Samuels et al 1990)

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 8: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

Phylogenetic tree representing all topotypes and lineages of serotype O with special emphasis on SEA

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 9: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Analysis of B cell epitope regions in VP1 protein – Site 3 Comparison with serotype O vaccine strains

Aktas & Samuel, 2000

Page 10: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Analysis of B cell epitope regions in VP1 protein – Site 1Comparison with serotype O vaccine strains

Aktas & Samuel, 2000

Page 11: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Analysis of B cell epitope regions in VP1 protein – Site 5Comparison with serotype O vaccine strains

Aktas & Samuel, 2000

Page 12: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

<0.2 – Heterologous; 0.2-0.39 – Intermediary; >0.39 – Homologous; Samuels et al 1990

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 13: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 14: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

2014 2015

Phylogenetic tree representing all topotypes and lineages of serotype A with special emphasis on SEA

Page 15: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

Analysis of B cell epitopes in the VP1 protein – Site 3Comparison with serotype A vaccine strains

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Baxt et al 1989

Page 16: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Baxt et al 1989

Analysis of B cell epitopes in the VP1 protein – Site 1Comparison with serotype A vaccine strains

Page 17: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Baxt et al 1989

Analysis of B cell epitopes in the VP1 protein – Site 5Comparison with serotype A vaccine strains

Page 18: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

Summary• Most of the viruses studied are homologous to the

serotype O and A vaccine strains used in Thailand

• Major changes noticed in the B-cell epitopes in the VP1 region – driven by vaccine pressure (?)

• Serotype O• O1 Manisa has a poor match with the isolates from SEA• Two sub-lineages of O Mya-98 identified in SEA since 2010• PanAsia1 also in circulation• Studies with O-3039 ongoing

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 19: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

Summary• Serotype A

• Three different variants of SEA-97 genotype identified

• 2014 & 2015 strains are divided into two sub-lineages

• Varying degrees of homology noticed against the different vaccine strains

• Isolates collected between 2010-2013 were heterologous to A MAY 97

• The current isolates (2014-2015) are intermediary or heterologous to A22 IRQ 64 and homologous to intermediary to A MAY 97

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 20: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

Continual monitoring of evolving strains in the SE Asia region, and their antigenic profile, is essential for preparedness, including maintaining the relevance of

vaccine banks

Samples received by SEA National labs & the OIE-RRL (Pakchong)

Potential threats currently not investigated

Surveillance: it’s what we don’t know that matters!

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

‘’Dark matter’’

Page 21: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

• Bottle necks• Remote areas• Lack of financial support• Real-time surveillance• Storage and buffers

• Need to identify alternative sample transport methods• Circumvent sample transportation buffer• Circumvent cold storage

– Filter paper cards– Lateral Flow Devices– Use of dry sample boxes (IATA approved)

Problems with sample flow into RRL, Thailand

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 22: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

• Vaccine matching studies using O-3039 to be fast-tracked

• Continued monitoring of serotype A essential

• Reagents for multiple vaccine strains in the region need to be organised

• Sample collection and transport methods need to be revisited to increase the surveillance for the disease

Conclusions

CSIRO - HEALTH & BIOSECURITY |AUSTRALIAN ANIMAL HEALTH LABORATORY

Page 23: VACCINE MATCHING AND GENETIC CHARACTERISATION OF FMDV SEROTYPE O AND A ISOLATES IN SOUTH - EAST ASIA Singanallur, Nagendrakumar 1 ; Seeyo, Kingkarn 2 ;

Thank youThank youFunding provided by:Meat and Livestock Australia and livestock industries: CCA Inc, ADF, ALFA, SCA, WPA, APL, GICA

“Within infinite myths lies the eternal truth; Who sees it all? The “Lord of Water” has but a thousand eyes,

The “Lord of heavens” has a hundred, And You and I, only two.

Collaboration with RRL, Packchong