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

12. 12
General strategy for the production of
recombinant capripoxvirus knock out
Johnston and McFadden. Cellular Microbiology (2004) 6:695-705

13. 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

14. 14
Generation of neutralizing antibodies in
vaccinated/unvaccinated sheep and goats

15. 15
IFN-γ(pg/ml)
14 days post-
vaccination
21 days post-
vaccination
Generation IFN-γ from PBMC’s of
vaccinated/unvaccinated goats

16. 16
Disease in vaccinated/unvaccinated sheep/goats following challenge

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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