sustainable food production: a lumpy skin disease virus (lsdv) deficient of a virulence factor...
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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 2014Theme: Enhancing Food Production
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- 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
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)
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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)
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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 cattleTransmission
- 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
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- 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
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From Truong et al. (2013)
Experimental Pathology of PPRV
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- 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
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General strategy for the production of recombinant capripoxvirus knock out
Johnston and McFadden. Cellular Microbiology (2004) 6:695-705
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- 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
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Generation of neutralizing antibodies in vaccinated/unvaccinated sheep and goats
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IFN
-γ (
pg
/ml)
14 days post-vaccination
21 days post-vaccination
Generation IFN-γ from PBMC’s of vaccinated/unvaccinated goats
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Disease in vaccinated/unvaccinated sheep/goats following challenge
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SheepA
Goats
Te
mp
era
ture
(o C
)T
em
pe
ratu
re (
o C)
Days post-challenge
Days post-challenge
B
Temperatures of vaccinated/unvaccinated sheep and goats following viral challenge with virulent
capripox
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Days post infection
Sheep
Goats
Days post infection
cop
ies/
mL
(lo
g 10)
cop
ies/
mL
(lo
g 10)
A
B
Viremia of vaccinated/unvaccinated sheep and goats following viral challenge with virulent
capripox
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- 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
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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
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
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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