WHICH VACCINES ARE MOST IMPORTANT?

PRAGMATIST: A DECISION SUPPORT TOOL FOR FOOT AND MOUTH DISEASE VACCINE BANK MANAGERS

Melissa McLaws1, Don King2, Katie Hickey1, Anna Ludi2, Keith Sumption1

European Commission for the Control of Foot and Mouth Disease (EuFMD) 1

WRLFMD The Pirbright Institute2

Key Messages

• PRAGMATIST is a tool to assist vaccine bank managers select /maintain the most appropriate antigens– Transparent, evidence based– Vaccine matching results

• Other applications:– Highlight data gaps and important antigens that do not have a

good vaccine available– Framework for surveillance to engage international FMD lab/epi

networks

• Next Steps– Ongoing efforts to improve data quality– User feedback

Context

• Viruses in any region are a potential threat to all other regions, no matter how far away, and consequently should be considered for inclusion in antigen banks. (Lombard & Füssel, 2007)

FMD serotypes

• FMD virus: 7 serotypes, multiple strains within serotypes.

• No cross-protection between serotypes – variable between strains within serotypes

• Multiple vaccine strains available

Context

• Viruses in any region are a potential threat to all other regions, no matter how far away, and consequently should be considered for inclusion in antigen banks. (Lombard & Füssel, 2007)

Which strains are most important to maintain in my vaccine bank?

• FMD virus: 7 serotypes, multiple strains within serotypes.

• No cross-protection between serotypes – variable between strains within serotypes

• Multiple vaccine strains available

Which strains to maintain in the vaccine bank?

• Significant financial investment• The World Reference Laboratory produces annual recommendations

– Antigens divided into high, medium and low priority – EU perspective: not “global” in nature– Criteria are not clearly defined

PRAGMATIST: PRioritisation of AntiGen MAnagemenT with International Surveillance Tool

• EuFMD and WRL collaboration • Assist risk managers make decisions about the FMD vaccines that

they purchase/maintain, based on current risks to countries covered by the bank

PRAGMATIST: Antigen Priority tool

• Excel spreadsheet• 2 distinct considerations:

1. “Antigen risk score”: which strains pose greatest threat of incursion (left side) and

2. “Coverage score”: effectiveness of available vaccines to protect against each virus strain (right side)

cv cv

Antigen risk score

• For a given free country/region the strains that pose the greatest threat of incursion will depend on:

1. From what FMD endemic area(s) is the virus most likely to enter the country? (most likely “source areas”)

2. Which virus strains are currently circulating in the source areas?

Where is the virus most likely to come from? (Source area score)

• Virus likely to enter due to illegal/informal activity– Legal activities made safe by border and trade restrictions

• Main routes of incursion:1. Infected live animals2. FMDV-contaminated animal product3. (Fomite, wildlife)

• Importance of the source area will depend on the user: – ie will be different if she is in Australia vs N. America vs.

Europe– Expert opinion/User inputConsider proximity, connectedness, incentive, prevalence

Where is the virus most likely to come from? (Source area score)

• Expert elicitation at European NRL meeting (May 2016)

Source Area MultiplierDivide 100 points according to the risk posed by the source areaW. Eurasia 41E. Asia 11N. Africa 25India & S. Asia 9East Africa 4West/Central Af 4Southern Africa 3S. America 3

100

Relative prevalence of viral strains circulating within the source areas

• Many virus pools have 3+ serotypes circulating at once, (& multiple strains within serotypes)

• Relative prevalence of serotypes/strains is dynamic:– population immunity (natural or

vaccination) – ecology of the viruses (eg new

strains outcompete older strains)

• Data: Submissions to WRL and expert opinion

𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑎𝑎 = �𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑎𝑎𝑠𝑠𝑠𝑠𝑎𝑎 1

𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑎𝑎𝑠𝑠𝑠𝑠𝑎𝑎 𝑛𝑛

𝑝𝑝𝑠𝑠𝑎𝑎𝑝𝑝𝑎𝑎𝑝𝑝𝑎𝑎𝑎𝑎𝑠𝑠𝑎𝑎 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑎𝑎 ∗ 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑎𝑎 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑎𝑎Calculating the Antigen risk score

Caution: Data preliminary, For example only!

Circulating StrainAntigen

score

source area score→ 41 11 25 9 4 4 3 3

O/ME-SA/PanAsia-2 30 1230 0 0 5 45 0 0 0 1275

O/ME-SA/PanAsia 10 410 10 110 0 0 0 0 0 0 520

O/SEA/Mya-98 0 32 352 0 0 0 0 0 0 352

O/ME-SA/Ind2001 5 205 3 33 24 600 90 810 0 0 0 0 1648

O/EA-3 0 0 54 1350 0 28 112 20 80 84 0 1434

O/EURO-SA 0 0 0 0 0 0 0 33 99.9 99.9

O/CATHAY 0 8 88 0 0 0 0 0 0 88

A/ASIA/Sea-97 0 36 396 0 0 0 0 0 0 396

A/ASIA/Iran-05 30 1230 0 15 375 0 0 0 0 0 1605

A/ASIA/G-VII 10 410 0 5 45 0 0 0 455

A/AFRICA 0 0 2 50 0 28 112 27 108 84 0 134

A/EURO-SA 0 0 0 0 0 0 0 33 99.9 99.9

Asia-1 0 11 121 0 0 0 0 0 0 121

Asia-1 Sindh-08 13 533 0 0 0 0 0 533

SAT1 0 0 0 0 8 32 26 104 40 24 0 24

SAT 2 2 82 0 5 125 0 28 112 25 100 40 84 0 291

SAT3 0 0 0 0 8 32 2 8 20 24 0 24

C 0 0 0 0 0 0 0 33 99.9 99.9

Cumulative Score 100 100 100 100 100 100 100 99.9 300

Score adjusted for route importance 4100 1100 2500 900 400 400 300 599

N. AfricaIndia & S.

AsiaS.

AmericaW.

Eurasia E. AsiaEast

Africa

West/ Central Africa

Southern Africa

PRAGMATIST: Antigen Priority tool

• Excel spreadsheet• 2 distinct considerations:

1. “Antigen risk score”: which strains pose greatest threat of incursion (left side) and

2. “Coverage score”: effectiveness of available vaccines to protect against each virus strain (right side)

cv cv

Coverage score

Coverage score

Vaccine Antigen coverage

no information0 no matching isolates

0.2 1-20% isolates match0.4 21-40% isolates match0.6 41-60% isolates match0.8 61-80% isolates match1 81-100% isolates match

• For each combination of vaccine and field virus strain• Percentage of isolates of that particular strain that match the vaccine in question

Caution: Data preliminary, For example only!

A22

Iraq

A24

Cruz

eiro

A-Ar

g/20

01

A-Er

itrea

A-Ira

n 96

A-Ira

n-05

A-M

alay

sai 9

7

A-SA

U 9

5

A-SA

U/2

3/86

A-TU

R/20

06

Mer

ial

MSD

Mer

ial

MSD

Mer

ial

Mer

ial

MSD

Mer

ial

Mer

ial

MSD

Mer

ial

MSD

MSD

0.6 0.4 0.2 0.60.4 0.2 0 0.2 0.2 0.6

0.6 0.4 0.4 0.4

SEROTYPE A

A/ASIA/Sea-97

A/ASIA/Iran-05

A/ASIA/G-VIIA/AFRICAA/EURO-SA

Putting it all together: vaccine score

High scores for vaccines that cover well against :

– Strains circulating in many areas and/or

– Strains in most important ‘risky’ areas and/or

– Several different strains

𝑝𝑝𝑎𝑎𝑠𝑠𝑠𝑠𝑎𝑎𝑎𝑎𝑎𝑎 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑎𝑎 = �𝑣𝑣𝑣𝑣𝑠𝑠𝑠𝑠𝑠𝑠 𝑠𝑠𝑠𝑠𝑠𝑠𝑎𝑎𝑣𝑣𝑛𝑛 1

𝑣𝑣𝑣𝑣𝑠𝑠𝑠𝑠𝑠𝑠 𝑠𝑠𝑠𝑠𝑠𝑠𝑎𝑎𝑣𝑣𝑛𝑛 𝑛𝑛

𝑠𝑠𝑠𝑠𝑝𝑝𝑎𝑎𝑠𝑠𝑎𝑎𝑎𝑎𝑎𝑎 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑎𝑎 ∗ 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑎𝑎

A22

Iraq

A24

Cruz

eiro

A-Ar

g/20

01

A-Er

itrea

A-Ira

n 96

A-Ira

n-05

A-M

alay

sai 9

7

A-SA

U 9

5

A-SA

U/2

3/86

A-TU

R/20

06

Mer

ial M

SD

Mer

ial M

SD

Mer

ial

Mer

ial

MSD

Mer

ial

Mer

ial M

SD

Mer

ial

MSD

MSD

0.6 0.4 0.2 0.60.4 0.2 0 0.2 0.2 0.6

0.6 0.4 0.4 0.4

960 0 0 375 0 533 400 0 0 1254

SEROTYPE A

A/ASIA/Sea-97

A/ASIA/Iran-05

A/ASIA/G-VIIA/AFRICAA/EURO-SA

Key Messages

• PRAGMATIST is a tool to assist vaccine bank managers select /maintain the most appropriate antigens– Transparent, evidence based– Vaccine matching results

• Other applications:– Highlight data gaps and important antigens that do not have a

good vaccine available– Framework for surveillance to engage international FMD lab/epi

networks

• Next Steps– Ongoing efforts to improve data quality– User feedback

Thank you for listening!