AN OVERVIEW OF REVERSE GENETIC APPROACHES TO … · vEGY VP3 SAT2 vEGY site3 SAT2 vEGY EHER SAT2...
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AN OVERVIEW OF REVERSE GENETIC APPROACHES TO ENHANCED FMD VACCINES
IN AFRICA
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FMD in South Africa
Physical barriers, like fences
Immune barrier using vaccination
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Endemic
cycle
Escape
Epidemic
cycle
Buffalo calves
African Buffalo herd
Other cloven-hooved animals
Livestock
Persistently
infected with
SAT viruses
Infection of
calves 6-18
months of age
The epidemiology of FMD in Africa is influenced
by two different patterns
Interaction between buffalo, FMDV and cattle
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Principles'of'Virology,'ASM'Press
Reverse genetics for FMDV
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Intra-serotype chimeric vaccine: clinical signs & viraemia
SAT2/ZIM/14/90
vSAT2
vSAT2ZIM14 -SAT2
A) Parental FMDV:
B) Chimeric FMDV constructs:
Vac
Vac
Chimera
Parental
Protected
ProtectedSevere tongue lesions 2 animals
High temperatures 2 animals
Systemic spread
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Energetically favorable binding of Heparin moiety
Chitray 2018 PhD
SAT2-SAT2 chimera with added
positive charges at 5-fold axis
CHO-K1
Time (Hours)
0
1
2
3
4
5
6
0 1 2 4 6 10 13 17 20 22 24
Tite
r(lo
g1
0)
Growth kinetics in BHK-21 suspension cells
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0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
0 7 14 21 28
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
0 7 14 21 28
SAT1 virus
SAT1/SAT2 chimera
B
C
Se
rum
tit
er
Se
rum
tit
er
Days post-vaccination
Days post-vaccination
0.6 ug
0.3 ug
1.2 ug
controls
0 2 4 7 11
16-1 0 3 1 0 0
16-2 0 1 0 0 0
16-3 0 0 0 0 0
16-4 0 1 0 0 0
16-5 0 1 1 0 0
11-1 0 10 9 2 2
11-2 0 13 9 5 2
6-1 0 5 2 0 0
6-2 0 3 1 0 0
6-3 0 0 0 0 0
6-4 0 0 0 0 0
6-5 0 0 0 0 0
13-1 0 0 0 0 0
13-2 0 5 3 0 0
13-3 0 0 0 0 0
13-4 0 0 0 0 0
13-5 0 0 0 0 0
14-1 0 0 0 0 0
14-2 0 0 0 0 0
14-3 0 0 0 0 0
14-4 0 0 0 0 0
14-5 0 0 0 0 0
11-3 0 10 9 2 2
11-4 0 13 9 5 2
8-1 0 0 0 0 0
8-2 0 0 0 0 0
8-3 0 0 0 0 0
8-4 0 0 0 0 0
8-5 0 0 0 0 0
5-1 0 0 1 1 0
5-2 0 0 0 0 0
5-3 0 0 1 1 0
5-4 0 0 0 0 0
5-5 0 0 0 0 0
1/4 Dose
1/16 Dose
Full
dose
Controls
1/4 Dose
1/16 Dose
Full
dose
Controls
SA
T1/S
AT
2 c
him
era
SA
T1
virus
Inter-serotype chimeric vaccine: Ab & clinical scores
Blignaut et al., 2011. J Virol.
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Interactions at the capsid 2-fold interface and stability
Kotecha et al., 2015. Nature Struct Mol Biol.
Scott et al., 2017. J Virol.
Scott et al., 2017. Vaccine.
2-fold axis
WT
93Y
