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

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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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)

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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