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The application of new vaccine
technologies to control high
consequence animal diseases
Bryan Charleston
• Inactivated
• Live attenuated
• Recombinant sub-unit
• Rationally attenuated
• RNA/ DNA vaccines
Veterinary Vaccines
Development
cost
BVDV
(Npro deletion + Rnase inactivation)
C Erns
Npro
Wild type
RNase neg.
+ Npro deletion
H349D
5 codons
C Erns
• Baculovirus expression VLP platform technology
• Builds on existing collaboration and substantial investment from Defra,
Wellcome, BMGF and MAH, to develop stabilised FMD VLPs for vaccination.
• Quadrivalent vaccine (O, A, SAT-1 and SAT-2 serotypes).
FMD VLP Vaccine
Respiratory Syncytial Virus Antigenic Site is Not Present in Post-fusion F
Pre-fusion Post-fusion
N
N
C
C
N
C
C
N
α4
α5post
Structural Vaccinology
ChAdOx1 for Rift Valley Fever
In use for other HUMAN vaccines
including COVID-19
Gn/Gc Genes
responsible for
immunity
RVF
Vir us
ChAdOx1
technology
+
Rift Valley Fever Non-
Replication Viral Vector
Vaccine (Zoonotic
Disease)
Modification of viral vector insert can significantly
improve immune responses
Mercado, N.B., Zahn, R.,
Wegmann, F. et al. Single-
shot Ad26 vaccine protects
against SARS-CoV-2 in
rhesus
macaques. Nature 586, 583
–588 (2020).
https://doi.org/10.1038/s415
86-020-2607-z
0 7 14 21 28 35 42 49 56
101
102
103
104
105
EPT
Boost
0 14 28 42 56
102
103
104
ND
50
Boost
0 7 14 21 28 35 42 49 56
101
102
103
104
105
Days post-immunisation
EPT
Boost
0 14 28 42 56
101
102
103
104
105
Days post-immunisation
ND
50
Boost
Prime-boost
Prime-only
ChAdOx1 nCoV-19 – antibody responses
RBD ELISA
pVNT
VNT
Graham et al., 2020
FL-S ELISA
RBD ELISA pVNT
RBD-SpyVLP - antibody responses
0 7 14 21 28 35 42 49 56
101
102
103
104
105
Days post-immunisation
RBD
EPT
Boost
0 7 14 21 28 35 42 49 56
102
103
104
Days post-immunisation
ND
50
Boost
21 35 56
101
102
103
104
105
Days post-immunisation
Boost
100g FL-S 5g RBD-VLP 50g RBD-VLP
VNT
Tan et al., 2020
Self amplifying SARS-CoV-2 vaccine
0 7 14 21 28 35 42 49 56
0
500
1000
1500
2000
2500
Days post-immunisation
IFN-
S-C/10
6
cells
Boost
0 7 14 21 28 35 42 49 56
101
102
103
104
Days post-immunisation
RBD
EPT
<
Boost
PC 0 7 14 21 28 35 42 49 56 PC
102
103
104
Days post-immunisation
ND
50
Boost
<101
35 56 35 56 35 56 35 56 35 56
101
102
103
Days post-immunisation
<
PC
0 7 21 35 49 56
0.0
0.5
1.0
1.5
2.0
Days post-immunisation
IFN-+TNF-+
cells
(%)
Boost
0 7 21 35 49 56
Days post-immunisation
Boost
10 g LNP-nCoVsaRNA
10 g LNP-nCoVsaRNA-02
1 g LNP-nCoVsaRNA-02
0.1 g LNP-nCoVsaRNA-02
ICS - CD4 T cells ICS - CD8 T cells
RBD ELISA pVNT VNT
IFN-γ ELISpot
Unpublished data
Pirbright Institute

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B. Charleston - The application of new vaccine technologies to control high consequence animal diseases

  • 1. The application of new vaccine technologies to control high consequence animal diseases Bryan Charleston
  • 2. • Inactivated • Live attenuated • Recombinant sub-unit • Rationally attenuated • RNA/ DNA vaccines Veterinary Vaccines Development cost
  • 3. BVDV (Npro deletion + Rnase inactivation) C Erns Npro Wild type RNase neg. + Npro deletion H349D 5 codons C Erns
  • 4. • Baculovirus expression VLP platform technology • Builds on existing collaboration and substantial investment from Defra, Wellcome, BMGF and MAH, to develop stabilised FMD VLPs for vaccination. • Quadrivalent vaccine (O, A, SAT-1 and SAT-2 serotypes). FMD VLP Vaccine
  • 5. Respiratory Syncytial Virus Antigenic Site is Not Present in Post-fusion F Pre-fusion Post-fusion N N C C N C C N α4 α5post Structural Vaccinology
  • 6. ChAdOx1 for Rift Valley Fever In use for other HUMAN vaccines including COVID-19 Gn/Gc Genes responsible for immunity RVF Vir us ChAdOx1 technology + Rift Valley Fever Non- Replication Viral Vector Vaccine (Zoonotic Disease)
  • 7. Modification of viral vector insert can significantly improve immune responses Mercado, N.B., Zahn, R., Wegmann, F. et al. Single- shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature 586, 583 –588 (2020). https://doi.org/10.1038/s415 86-020-2607-z
  • 8. 0 7 14 21 28 35 42 49 56 101 102 103 104 105 EPT Boost 0 14 28 42 56 102 103 104 ND 50 Boost 0 7 14 21 28 35 42 49 56 101 102 103 104 105 Days post-immunisation EPT Boost 0 14 28 42 56 101 102 103 104 105 Days post-immunisation ND 50 Boost Prime-boost Prime-only ChAdOx1 nCoV-19 – antibody responses RBD ELISA pVNT VNT Graham et al., 2020 FL-S ELISA
  • 9. RBD ELISA pVNT RBD-SpyVLP - antibody responses 0 7 14 21 28 35 42 49 56 101 102 103 104 105 Days post-immunisation RBD EPT Boost 0 7 14 21 28 35 42 49 56 102 103 104 Days post-immunisation ND 50 Boost 21 35 56 101 102 103 104 105 Days post-immunisation Boost 100g FL-S 5g RBD-VLP 50g RBD-VLP VNT Tan et al., 2020
  • 10. Self amplifying SARS-CoV-2 vaccine 0 7 14 21 28 35 42 49 56 0 500 1000 1500 2000 2500 Days post-immunisation IFN- S-C/10 6 cells Boost 0 7 14 21 28 35 42 49 56 101 102 103 104 Days post-immunisation RBD EPT < Boost PC 0 7 14 21 28 35 42 49 56 PC 102 103 104 Days post-immunisation ND 50 Boost <101 35 56 35 56 35 56 35 56 35 56 101 102 103 Days post-immunisation < PC 0 7 21 35 49 56 0.0 0.5 1.0 1.5 2.0 Days post-immunisation IFN-+TNF-+ cells (%) Boost 0 7 21 35 49 56 Days post-immunisation Boost 10 g LNP-nCoVsaRNA 10 g LNP-nCoVsaRNA-02 1 g LNP-nCoVsaRNA-02 0.1 g LNP-nCoVsaRNA-02 ICS - CD4 T cells ICS - CD8 T cells RBD ELISA pVNT VNT IFN-γ ELISpot Unpublished data