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

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  • 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. 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. 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 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
  • 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
  • 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 From Truong et al. (2013) Experimental Pathology of PPRV
  • 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. 12 General strategy for the production of recombinant capripoxvirus knock out Johnston and McFadden. Cellular Microbiology (2004) 6:695-705
  • 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. 14 Generation of neutralizing antibodies in vaccinated/unvaccinated sheep and goats
  • 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. 16 Disease in vaccinated/unvaccinated sheep/goats following challenge
  • 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. 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. 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. 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. 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. 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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