A lumpy skin disease virus (LSDV)
deficient of a virulence factor provides
complete protection against virulent
capripoxvi...
22
- 300 million people on the African continent are
dependent on livestock for their livelihood (AU-
IBAR); of particular...
Solution
- Vaccination is the solution
- Currently live attenuated vaccines are used for
sheep and goat pox, lumpy skin di...
4
Clinical disease
- Fever, lack of appetite, painful swelling, lacrimation
and swollen eyelids, mucopurulent discharge, c...
5
6
Lumpy skin disease (capripoxvirus)
Clinical disease
- Pyrexia, skin lesions: head, flank, perineum hides are
destroyed, ...
7
8
- An acute, contagious and frequently fatal disease of goats and
sheep characterised by fever, ocular and nasal discharg...
9
From Truong et al. (2013)
Experimental Pathology of PPRV
10
- A disease that causes fever, inappetence, mucopurulent
nasal discharge, bloody diarrhea
- 90 - 100% of pregnant anima...
12
General strategy for the production of
recombinant capripoxvirus knock out
Johnston and McFadden. Cellular Microbiology...
13
- Minor injection site redness, which was absent 21
days following vaccination
- No replication of attenuated virus was...
14
Generation of neutralizing antibodies in
vaccinated/unvaccinated sheep and goats
15
IFN-γ(pg/ml)
14 days post-
vaccination
21 days post-
vaccination
Generation IFN-γ from PBMC’s of
vaccinated/unvaccinate...
16
Disease in vaccinated/unvaccinated sheep/goats following challenge
17
SheepA
Goats
Temperature
(o
C)
Temperature
(o
C)
Days post-challenge
Days post-challenge
B
Temperatures of vaccinated/u...
18
Days post infection
Sheep
Goats
Days post infection
copies/mL(log10)copies/mL(log10)
A
B
Viremia of vaccinated/unvaccin...
19
- An attenuated LSDV KO vaccine provides protection against
sheep and goat pox
- No clinical signs were observed in vac...
20
0 150 000 bp
Fp7.5K GcGn
PPRV
RVFV
ORF KO L p7.5K
LSDV genome
LSDV-vectored PPRV-RFV construct
(1 insertion site)
ORF K...
212121
- Evaluate safety and efficacy of the multivalent LSDV vaccine in
sheep and goats against:
i) Virulent sheep and go...
2222
Acknowledgements
IDRC/DFATD as the sponsor for the conference
University of Alberta as the host for the conference
Fu...
Sustainable Food Production: A lumpy skin disease virus (LSDV) deficient of a virulence factor provides complete protectio...
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Sustainable Food Production: A lumpy skin disease virus (LSDV) deficient of a virulence factor provides complete protection against virulent capripoxvirus challenge

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Sustainable Food Production: A lumpy skin disease virus (LSDV) deficient of a virulence factor provides complete protection against virulent capripoxvirus challenge

  1. 1. A lumpy skin disease virus (LSDV) deficient of a virulence factor provides complete protection against virulent capripoxvirus challenge Project team: Vaccines to combat livestock diseases in sub-Saharan Africa International Food Security Dialogue 2014 Theme: Enhancing Food Production
  2. 2. 22 - 300 million people on the African continent are dependent on livestock for their livelihood (AU- IBAR); of particular importance are small ruminant livestock - The livestock industry in Africa has to deal will multiple endemic diseases: Damage inflicted by diseases account for up to 25% of all livestock losses (ILRI-AGRA) - Sheep and goat pox, lumpy skin disease (cattle), peste des petits ruminants and Rift Valley fever cause great economic losses to the agriculture industry in Africa Problem
  3. 3. Solution - Vaccination is the solution - Currently live attenuated vaccines are used for sheep and goat pox, lumpy skin disease, peste de petits ruminants, and Rift Valley fever - Only sheep and goat pox and lumpy skin disease vaccines are thermo-stable - Developing a thermo-stable multivalent vaccine based on a lumpy skin disease vaccine to protect against multiple viral pathogens (LSDV, sheep and goat pox, PPRV, RVFV) would be an economical benefit to the livestock industry (LSDV, sheep and goat pox, PPRV, RVFV) 3
  4. 4. 4 Clinical disease - Fever, lack of appetite, painful swelling, lacrimation and swollen eyelids, mucopurulent discharge, crusts nasal discharge, hypersalivation, followed by skin eruptions, pain Transmission - Contact with infected animals - Aerosol transmission - Contact with infected wool or bedding - Insect vectors biting flies mosquitoes likely can act as vectors but it is not proven - Virus is stable in the environment for weeks Sheep and goat pox (capripoxvirus)
  5. 5. 5
  6. 6. 6 Lumpy skin disease (capripoxvirus) Clinical disease - Pyrexia, skin lesions: head, flank, perineum hides are destroyed, ocular and nasal discharge - Infection of mucus membranes results in urinary track infection, abortion and mastitis - Disease is highly variable in the severity of disease that develop in cattle Transmission - Mode of transmission has not been established fully but biting insects are believed to play a major role - Not infectious without the vector Influences affecting transmission - Spread along watercourses and during the wet season - Periodic epidemics occur in most African countries
  7. 7. 7
  8. 8. 8 - An acute, contagious and frequently fatal disease of goats and sheep characterised by fever, ocular and nasal discharges, oral erosions, diarrhoea and pneumonia - Cause: a morbillivirus (PPRV) - Transmission is mainly by aerosols between animals living in close contact - Very little spread over distance without animal movement - Host range is limited: Sheep and goats - An experimental infection model was developed for both sheep and goats (Truong et al. 2013) Peste des petits ruminants
  9. 9. 9 From Truong et al. (2013) Experimental Pathology of PPRV
  10. 10. 10 - A disease that causes fever, inappetence, mucopurulent nasal discharge, bloody diarrhea - 90 - 100% of pregnant animals abort - 90% mortality in lambs/kids within 36 hrs after the onset of signs 20 - 60% mortality in adult animals - Cause: Bunyaviridae (Phlebovirus) - Transmission is by insect vectors mosquitoes - Host range is: sheep, goats, cattle, camels (and is zoonotic) Rift Valley fever
  11. 11. 12 General strategy for the production of recombinant capripoxvirus knock out Johnston and McFadden. Cellular Microbiology (2004) 6:695-705
  12. 12. 13 - Minor injection site redness, which was absent 21 days following vaccination - No replication of attenuated virus was detected in oral and nasal swabs as well as whole blood (as detected by real-time PCR) - Serology confirmed that the vaccine generated antibodies - Cell-mediated immunity was measured using antigen recall responses Safety and immunogenicity of a LSDV KO vaccine in sheep and goats
  13. 13. 14 Generation of neutralizing antibodies in vaccinated/unvaccinated sheep and goats
  14. 14. 15 IFN-γ(pg/ml) 14 days post- vaccination 21 days post- vaccination Generation IFN-γ from PBMC’s of vaccinated/unvaccinated goats
  15. 15. 16 Disease in vaccinated/unvaccinated sheep/goats following challenge
  16. 16. 17 SheepA Goats Temperature (o C) Temperature (o C) Days post-challenge Days post-challenge B Temperatures of vaccinated/unvaccinated sheep and goats following viral challenge with virulent capripox
  17. 17. 18 Days post infection Sheep Goats Days post infection copies/mL(log10)copies/mL(log10) A B Viremia of vaccinated/unvaccinated sheep and goats following viral challenge with virulent capripox
  18. 18. 19 - An attenuated LSDV KO vaccine provides protection against sheep and goat pox - No clinical signs were observed in vaccinated animals following: a) vaccination, and; b) viral challenge using virulent sheep or goat pox - Immunity was achieved by a mixture of both antibody as well as cell-mediated immunityLack of viremia, as well as lack of pox lesions suggests near-sterile immunity in both sheep and goats - Safety and efficacy of this vaccine strain, in combination with the ability to insert foreign antigens, suggests that a multivalent vaccine is plausible Conclusions
  19. 19. 20 0 150 000 bp Fp7.5K GcGn PPRV RVFV ORF KO L p7.5K LSDV genome LSDV-vectored PPRV-RFV construct (1 insertion site) ORF KO R ORF KO
  20. 20. 212121 - Evaluate safety and efficacy of the multivalent LSDV vaccine in sheep and goats against: i) Virulent sheep and goat pox ii) RVFV challenge iii) PPRV - Evaluate safety and efficacy of the multivalent LSDV vaccine in cattle against: i) Virulent LSDV ii) RVFV challenge - Field trials and vaccine licensing Future Directions
  21. 21. 2222 Acknowledgements IDRC/DFATD as the sponsor for the conference University of Alberta as the host for the conference Funding - Canadian International Food Security Research Fund Vaccines to combat livestock diseases in sub-Saharan Africa (106930) NCFAD (Winnipeg) Shawn Babiuk, Charles Nfon, Thang Truong Animal care: Kurtis Swekla, Marlee Phair, Maggie Forbes, Cory Nakamura, Jaime Bernstein Pathology: Carissa Embury-Hyatt, Brad Collignon, Jill Graham, Estella Moffat ARC-OVI (South Africa) David Wallace, Arshad Mather, Pravesh Kara, Thireshni Chetty, Livio Heath VIDO (University of Saskatchewan) Volker Gerdts, Suresh Tikoo University of Alberta Lorne Babiuk
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