foot-and-mouth disease virus: linking transmission
TRANSCRIPT
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Foot-and-mouth disease virus:
linking transmission pathogenesis
and immunology
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Transmission study
2 days later 4 days later 6 days later 48 hrs
inoculates
challenged donors
direct contact recipients
Animals monitored for
14 days post-challenge
In contact
for 24 hrs
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FMDV transmission biology
Probang
Nasal swab
Blood
Transmission
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Type 1 interferon production (donors)
0
2
4
6
8
10
12
14
0 1 2 3 4 5 6 7 8
Days post infection
U/m
l VN89
VN90
Clinical score VS study day
0
2
4
6
8
10
12
D-2 D-1 D0 D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11 D12 D13 D14 D15 D16 D17 D18 D19 D20
Study day
Clin
ica
l s
co
re
VN89
VN90
Type 1 Interferon is found in sera of FMDV infected cattle
at the onset of clinical signs
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Data.038
CD172a on CD4+/CD3-
(100,000) stimulated cells
FL2-HC
ount
100
101
102
103
104
0
5
10
15
20
Data.039
MHC II on CD4+/CD3-
(100,000) stimulated cells
FL2-H
Count
100
101
102
103
104
0
5
10
15
20
Data.040
CD11c on CD4+/CD3-
(100,000) stimulated cells
FL2-H
Count
100
101
102
103
104
0
5
10
15
20
Data.042
CD45RB on CD4+/CD3-
(100,000) stimulated cells
FL2-H
Count
100
101
102
103
104
0
5
10
15
20Data.030
FL1-H
FL4-
H
100
101
102
103
104
100
101
102
103
104
13.85%68.18%
16.11%1.85%
CD3
CD 172a MHC II CD 11c CD 45RB
Induction of type-1 interferon by bovine plasmacytoid dendritic cells (pDCs) in response to foot-and-mouth disease virus
Data.005
CD3
CD4
100
101
102
103
104
100
101
102
103
104
Gate 2
4.64%
Gate 2
4.64% 8.88%
79.52% 6.97%
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Is the virus entering the cell via the FC receptor? Use antibodies to CD 32 (FC receptor) to block entry
O1K alone O1K+IC
with isotype control
O1K+IC
blocked with anti CD32
Non-structural protein
FMDV capsid protein
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0
50
100
150
200
250
300
Medium O1-BFS O1-BFS + immune
IgG
O1-BFS UV O1-BFS UV +
immune IgG
Co
un
ts p
er
min
ute
x 1
03
*
Dendritic cell targeting of FMDV antigen can be improved
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Immune response to vaccination rapid induction of antibody variable/ short duration of immunity variable CD4 T cell response
Foot-and-mouth disease virus
Immune response to infection rapid induction of antibody prolonged duration of immunity modest CD4 T cell response
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FMDV capsid: T independent and T dependent epitopes
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-50
0
50
100
150
200
250
300
350
400
450
500
-1 0 1 2 3 4 5 6 7 9 13 16 21
Control group
Depleted group
Effect of CD4 T cell response on
neutralising antibody response to
vaccination
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Persistence of FMDV antigen
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4 µm DAPI CD21 FMDV
No expression of non-structural proteins: -Non-replicating -Extracellular
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FMDV capsid protein in mouse spleen GC
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Structural analysis at the Diamond light source
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Structure-based stabilisation of FMDV capsids
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Structure-based stabilisation of FMDV capsids
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Sum average of aligned images
Capsid stable at 55oC or pH5 for 2 hours
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A22_H93C combined – 2 A22_H93C combined – 2
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0
200
400
600
800
1000
1200
1400
An
tib
od
y T
itre
Week
Group 1 - Baculovirus WT A capsid
FMD 140
FMD 141
FMD 142
FMD 143
0
200
400
600
800
1000
1200
1400
An
tib
od
y T
itre
Week
Group 2 - Baculovirus mt A capsid
FMD 144
FMD 145
FMD 146
FMD 147
Cattle vaccinated with 12ug of Baculovirus derived FMDV
capsids in commercial oil adjuvant Day 0 and Day 21
0
20000
40000
60000
80000
100000
120000
Media BHK-21 1ug/ml A22 wt Vaccinia
capsid (1μg/ml)
Day 42
WT
mt A
T cell response
Antibody titre
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- Stabilise antigen (Persistence of antigen)
- Target antigen - Provide co-stimulation (Danger signals)
Vaccination
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Nick Juleff
Julian Seago
Lucy Robinson
Kerry Mclaughlin
Liz Reid
Miriam Windsor
Terry Jackson
Claudine Porta
Dave Stuart
Liz Fry
Ivan Morrison
Mark Woolhouse
Roy Bengis
Francois Maree