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!