Download Production and evaluation of FMDV stabilised capsids as potent, rapidly deployable vaccines, B. Charleston

Bryan Charleston
Global Foot-and-mouth disease Research Alliance (GFRA):
Production and evaluation of Foot-and-mouth disease virus stabilised capsids
as potent, rapidly deployable vaccines
“emergency vaccination should be seen as a major tool of first resort …
for controlling FMD outbreaks”
Royal Society
Recombinant FMDV
capsids
Translation strategy – selectively reduce 3C
translation
142C>T/S
mRNA levels unaltered
Baculovirus derived FMDV capsids
Structure-based stabilisation of FMDV capsids
Proof of principle that an engineered mutation (his to cys) is
consistent with capsid assembly.
Similar approaches can be used for infectious copies.
Structure-based stabilisation of FMDV capsids
Proof of principle that an engineered mutation (his to cys) is
consistent with capsid assembly.
Similar approaches can be used for infectious copies.
Capsid production2
Wild-type and stable capsid
structures2
Empty capsids with enhanced stability
Cattle vaccinated with 12ug of Baculovirus derived FMDV
capsids in commercial oil adjuvant Day 0 and Day 21
Stabilised empty capsids
- Improved storage characteristics: vaccine ready for deployment, less reliant on
cold chain
- Safe production: no live virus required, enhanced production capacity
- Vaccine can be produced to new virus variants: no need to isolate virus
and adapt to tissue culture, sequence → gene synthesis → expression
- Opportunities for further development: enhance early response,
increased antigenic breadth
- No non-structural proteins: companion DIVA diagnostic tests, greater certainty
of discriminating between vaccinated and infected animals
- Reagents for diagnostic test: safe production, improved shelf life
Julian Seago
Nick Juleff
Terry Jackson
Claudine Porta
Dave Stuart
Liz Fry
Abhay Kotecha
Francois Maree
Belinda Blignaut
Katherine Scott
Pamela Opperman
Elizabeth Rieder
Sabena Uddowla
Ian Jones