1.
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

2.
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

3.
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

4.
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

5.
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

6.
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

7.
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

8.
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?

9.
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 animals
2. FMDV-contaminated animal product
3. (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 input
Consider proximity, connectedness, incentive, prevalence

10.
Where is the virus most likely to come from?
(Source area score)
• Expert elicitation at European NRL meeting (May 2016)
Source Area Multiplier
Divide 100 points according to the risk posed by the source area
W. Eurasia 41
E. Asia 11
N. Africa 25
India & S. Asia 9
East Africa 4
West/Central Af 4
Southern Africa 3
S. America 3
100

11.
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

12.
𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑎𝑎𝑎𝑎𝑎𝑎 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 = �
𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 1
𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑛𝑛
𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 ∗ 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠Calculating the
Antigen risk score
Caution: Data preliminary, For example only!
Circulating Strain
Antigen
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. Africa
India & S.
Asia
S.
America
W.
Eurasia E. Asia
East
Africa
West/
Central
Africa
Southern
Africa

13.
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

14.
Coverage score
Coverage
score
Vaccine Antigen coverage
no information
0 no matching isolates
0.2 1-20% isolates match
0.4 21-40% isolates match
0.6 41-60% isolates match
0.8 61-80% isolates match
1 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

15.
Caution: Data preliminary, For example only!
A22Iraq
A24Cruzeiro
A-Arg/2001
A-Eritrea
A-Iran96
A-Iran-05
A-Malaysai97
A-SAU95
A-SAU/23/86
A-TUR/2006
Merial
MSD
Merial
MSD
Merial
Merial
MSD
Merial
Merial
MSD
Merial
MSD
MSD
0.6 0.4 0.2 0.6
0.4 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-VII
A/AFRICA
A/EURO-SA

16.
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
𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 = �
𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 1
𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑛𝑛
𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 ∗ 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑎𝑎𝑎𝑎𝑎𝑎 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠
A22Iraq
A24Cruzeiro
A-Arg/2001
A-Eritrea
A-Iran96
A-Iran-05
A-Malaysai97
A-SAU95
A-SAU/23/86
A-TUR/2006
MerialMSD
MerialMSD
Merial
Merial
MSD
Merial
MerialMSD
Merial
MSD
MSD
0.6 0.4 0.2 0.6
0.4 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-VII
A/AFRICA
A/EURO-SA

17.
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

18.
Thank you for listening!