défis scientifiques et economiques du développement de vaccins...
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Deacutefis Scientifiques et
Economiques du Deacuteveloppement
de Vaccins
pour les Pays du Sud
maladies animales et
zoonotiques
Thierry Lefranccedilois Franccedilois Thiaucourt
Renaud Lancelot
UMR Cirad-Inra CMAEE
laquo Controcircle des maladies animales exotiques
et eacutemergentes raquo
2 deacutecembre 2015
Targ
et
Disease
prevention
Disease
treatment
Management
and hygiene
Kn
ow
led
ge
atti
tud
es
per
cep
tio
n
Rea
sear
ch
pro
du
cts
New or
improved
Vaccines
Vaccine
use
New
improved
Treatments
Therapy use
Res
earc
h
area
s Vaccinology
immunology
Omics
Socio-
economics
Policy
delivery
Ou
tco
me
Delivery and adoption of technologies and information regulatory issues for TADs
Epidemiology economics
and impact assessment
In silico models
Poor livestock keepers
Disease control strategies
Vaccine development and control strategies
Adapted from expert consultation organized by ILRI in 2002 Perry BD Randolph TF McDermott JJ Sones KR and Thornton PK
2002 Investing in animal health research to alleviate poverty ILRI (International Livestock
Research Institute) Nairobi Kenya 148 pp
httpswwwilriorgInfoServWebpubfulldocsinvestinginAnimalBook1media
Challenges in epidemiology
establish needs and baseline data
Notification distribution example of Contagious bovine
pleuropneumonia (CBPP)
OIE Jan-Jun 2015
OIE Jul-Dec 2015
Seacutery A Sidibeacute C Cisseacute O Diallo M
Koneacute M Waret-Szkuta A Roger F
Thiaucourt F Niang M 2014
Seroprevalence of contagious bovine
pleuropneumonia (CBPP) in Mali Tropical
Animal Health and Production1-8
Impact assessment and research opportunities
Vaccine research
activities may be
based on expert
consultations
Priorities may vary
a lot between and
within a region
Expert review or
regional
workshops in
2002
Zoonotic diseases
New
vaccines
Modified
vaccines
Diagnostic Epidemiology Delivery
extension
1 Brucella abortus
2 Brucella melitensis
3 Trypanosomosis
4 Bovine tuberculosis
5 Leptospirosis
6 Anthrax
7 Cysticercosis
8 Buffalo pox
9 Rift Valley Fever
10 Toxocara vitulorum
11 Cysticercus bovis
12 Japanese B encephalitis
13 Schistosomosis
14 Botulism
15 Trichinella
16 Mange
17 Brucella suis
18 Rabies
19 Orf
What is needed for a vaccine
define research questions
Product Induction of solid immunity to re-infection
Duration of vaccinal immunityrequirement for administration of booster vaccinations
Safety
Thermostability
Markers to differenciate vaccinated from infected animals (DIVA)
Universality of protection (Antigenic variations in the pathogen)
Compatibility with other vaccines (multivalent vaccines or concomitant administration)
Production Amenability to large scale production
Cost of vaccine production and control
Delivery Quality of the supply chain
Cost of delivery systems
Acceptability by owners (Knowledgeacceptabilitypractices))
Competition with other control measures (antibiotics anti vector fight)
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments)
Specificities for the South andor for animals
Triggering a protective immune response
African swine fever
Need more
research
Modern adjuvants do not enhance the
efficacy of an inactivated African swine fever
virus vaccine preparation Blome S et al
Vaccine 2014
African Swine Fever Virus Georgia 2007 with
a Deletion of Virulence-Associated Gene 9GL
(B119L) when Administered at Low Doses
Leads to Virus Attenuation in Swine and
Induces an Effective Protection against
Homologous Challenge ODonnell V et al J
Virol 2015
Enhance the duration of immunity
CBPP
Mathematical modelling of the
transmission dynamics of
contagious bovine
pleuropneumonia reveals minimal
target profiles for improved
vaccines and diagnostic assays
Ssematimba A et al PLoS One 2015
Cheap existing vaccines
Not thermostable
Protection for 6 months (T1sr) to one year (T144)
Owners may prefer treating their animals with antibiotics
Target profile protection duration gt 2 years
bull Mutant library used to select one mutant in immuno-dominant antigen
bull Antibiotic selection marker removed + inactivation of antigen
bull Incorporation into water-in-oil emulsion preparation (Seppic)
bull increased thermostability
bull Laboratory trials in Bamako Mali good protection after 6 months
bull Adjuvant compatible with other vaccines Heartwater FMDhellip
Overcome protection failure Newcastle disease
Proteacuteine F aa 33-454 trimegravere
(a) Vu de la tecircte par le dessus
(b) Vu laterale
(a) (b)
All vaccines based on 50 year old strains
Did African strains derived
Wild and domestic bird surveillance in Africa
bull 13 000 samples
bull isolation and sequencing of 110 genomes
bull new genotypes amp phylogeographic study
bull divergences between these genotypes
and vaccine (14 substitutions in immunodominant areas)
Epitope mapping
Produce a cheap and ready to use vaccine
Heartwater
Perspectives
Cocktail of strains adapted regionaly for better cross protection
MAP1-related proteins
118+19+2025 3436384142675556
213743+44+45+46+6248+53T4SS
3551+52
Protein turnover processes
Chaperones
59274965
Proteinprocessing
and turnover
1757
Cell redox homeostatis
58+59 54
Amino acids
Fatty acids
Nucleotide
Pyrimidine
Purine
Pentose phosphate
GlycolysisTerpenoidSteroids
Glycerophospholipid
UbiquinoneHeme
SerGly PyruvateCysArg
Asp
Pro Gln
Glu
CofactorsCofactors
Glyoxylate
Folate (VitB9)
Oxidative phosphorylation
Orn
Lys
Tyr
Phe
63 268
4047
40
10
23
6+7
TCA cycle 4
24613
28+29+30+31
3322
Information processes
DNA Transcription
2 68
DNA replication
13+14 66
Translation
8 11 39 50+60
Hypothetical proteins
Back to fundamental studies Heartwater
Virulence mechanisms laquoomicsraquo bioinformatics amp functionnal studies
In vitro model for virulent amp attenuated strains
Transcriptomic amp proteomics of E ruminantium
SST4 effectors
1 Software SATE
2 Functionnal validation
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Targ
et
Disease
prevention
Disease
treatment
Management
and hygiene
Kn
ow
led
ge
atti
tud
es
per
cep
tio
n
Rea
sear
ch
pro
du
cts
New or
improved
Vaccines
Vaccine
use
New
improved
Treatments
Therapy use
Res
earc
h
area
s Vaccinology
immunology
Omics
Socio-
economics
Policy
delivery
Ou
tco
me
Delivery and adoption of technologies and information regulatory issues for TADs
Epidemiology economics
and impact assessment
In silico models
Poor livestock keepers
Disease control strategies
Vaccine development and control strategies
Adapted from expert consultation organized by ILRI in 2002 Perry BD Randolph TF McDermott JJ Sones KR and Thornton PK
2002 Investing in animal health research to alleviate poverty ILRI (International Livestock
Research Institute) Nairobi Kenya 148 pp
httpswwwilriorgInfoServWebpubfulldocsinvestinginAnimalBook1media
Challenges in epidemiology
establish needs and baseline data
Notification distribution example of Contagious bovine
pleuropneumonia (CBPP)
OIE Jan-Jun 2015
OIE Jul-Dec 2015
Seacutery A Sidibeacute C Cisseacute O Diallo M
Koneacute M Waret-Szkuta A Roger F
Thiaucourt F Niang M 2014
Seroprevalence of contagious bovine
pleuropneumonia (CBPP) in Mali Tropical
Animal Health and Production1-8
Impact assessment and research opportunities
Vaccine research
activities may be
based on expert
consultations
Priorities may vary
a lot between and
within a region
Expert review or
regional
workshops in
2002
Zoonotic diseases
New
vaccines
Modified
vaccines
Diagnostic Epidemiology Delivery
extension
1 Brucella abortus
2 Brucella melitensis
3 Trypanosomosis
4 Bovine tuberculosis
5 Leptospirosis
6 Anthrax
7 Cysticercosis
8 Buffalo pox
9 Rift Valley Fever
10 Toxocara vitulorum
11 Cysticercus bovis
12 Japanese B encephalitis
13 Schistosomosis
14 Botulism
15 Trichinella
16 Mange
17 Brucella suis
18 Rabies
19 Orf
What is needed for a vaccine
define research questions
Product Induction of solid immunity to re-infection
Duration of vaccinal immunityrequirement for administration of booster vaccinations
Safety
Thermostability
Markers to differenciate vaccinated from infected animals (DIVA)
Universality of protection (Antigenic variations in the pathogen)
Compatibility with other vaccines (multivalent vaccines or concomitant administration)
Production Amenability to large scale production
Cost of vaccine production and control
Delivery Quality of the supply chain
Cost of delivery systems
Acceptability by owners (Knowledgeacceptabilitypractices))
Competition with other control measures (antibiotics anti vector fight)
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments)
Specificities for the South andor for animals
Triggering a protective immune response
African swine fever
Need more
research
Modern adjuvants do not enhance the
efficacy of an inactivated African swine fever
virus vaccine preparation Blome S et al
Vaccine 2014
African Swine Fever Virus Georgia 2007 with
a Deletion of Virulence-Associated Gene 9GL
(B119L) when Administered at Low Doses
Leads to Virus Attenuation in Swine and
Induces an Effective Protection against
Homologous Challenge ODonnell V et al J
Virol 2015
Enhance the duration of immunity
CBPP
Mathematical modelling of the
transmission dynamics of
contagious bovine
pleuropneumonia reveals minimal
target profiles for improved
vaccines and diagnostic assays
Ssematimba A et al PLoS One 2015
Cheap existing vaccines
Not thermostable
Protection for 6 months (T1sr) to one year (T144)
Owners may prefer treating their animals with antibiotics
Target profile protection duration gt 2 years
bull Mutant library used to select one mutant in immuno-dominant antigen
bull Antibiotic selection marker removed + inactivation of antigen
bull Incorporation into water-in-oil emulsion preparation (Seppic)
bull increased thermostability
bull Laboratory trials in Bamako Mali good protection after 6 months
bull Adjuvant compatible with other vaccines Heartwater FMDhellip
Overcome protection failure Newcastle disease
Proteacuteine F aa 33-454 trimegravere
(a) Vu de la tecircte par le dessus
(b) Vu laterale
(a) (b)
All vaccines based on 50 year old strains
Did African strains derived
Wild and domestic bird surveillance in Africa
bull 13 000 samples
bull isolation and sequencing of 110 genomes
bull new genotypes amp phylogeographic study
bull divergences between these genotypes
and vaccine (14 substitutions in immunodominant areas)
Epitope mapping
Produce a cheap and ready to use vaccine
Heartwater
Perspectives
Cocktail of strains adapted regionaly for better cross protection
MAP1-related proteins
118+19+2025 3436384142675556
213743+44+45+46+6248+53T4SS
3551+52
Protein turnover processes
Chaperones
59274965
Proteinprocessing
and turnover
1757
Cell redox homeostatis
58+59 54
Amino acids
Fatty acids
Nucleotide
Pyrimidine
Purine
Pentose phosphate
GlycolysisTerpenoidSteroids
Glycerophospholipid
UbiquinoneHeme
SerGly PyruvateCysArg
Asp
Pro Gln
Glu
CofactorsCofactors
Glyoxylate
Folate (VitB9)
Oxidative phosphorylation
Orn
Lys
Tyr
Phe
63 268
4047
40
10
23
6+7
TCA cycle 4
24613
28+29+30+31
3322
Information processes
DNA Transcription
2 68
DNA replication
13+14 66
Translation
8 11 39 50+60
Hypothetical proteins
Back to fundamental studies Heartwater
Virulence mechanisms laquoomicsraquo bioinformatics amp functionnal studies
In vitro model for virulent amp attenuated strains
Transcriptomic amp proteomics of E ruminantium
SST4 effectors
1 Software SATE
2 Functionnal validation
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Challenges in epidemiology
establish needs and baseline data
Notification distribution example of Contagious bovine
pleuropneumonia (CBPP)
OIE Jan-Jun 2015
OIE Jul-Dec 2015
Seacutery A Sidibeacute C Cisseacute O Diallo M
Koneacute M Waret-Szkuta A Roger F
Thiaucourt F Niang M 2014
Seroprevalence of contagious bovine
pleuropneumonia (CBPP) in Mali Tropical
Animal Health and Production1-8
Impact assessment and research opportunities
Vaccine research
activities may be
based on expert
consultations
Priorities may vary
a lot between and
within a region
Expert review or
regional
workshops in
2002
Zoonotic diseases
New
vaccines
Modified
vaccines
Diagnostic Epidemiology Delivery
extension
1 Brucella abortus
2 Brucella melitensis
3 Trypanosomosis
4 Bovine tuberculosis
5 Leptospirosis
6 Anthrax
7 Cysticercosis
8 Buffalo pox
9 Rift Valley Fever
10 Toxocara vitulorum
11 Cysticercus bovis
12 Japanese B encephalitis
13 Schistosomosis
14 Botulism
15 Trichinella
16 Mange
17 Brucella suis
18 Rabies
19 Orf
What is needed for a vaccine
define research questions
Product Induction of solid immunity to re-infection
Duration of vaccinal immunityrequirement for administration of booster vaccinations
Safety
Thermostability
Markers to differenciate vaccinated from infected animals (DIVA)
Universality of protection (Antigenic variations in the pathogen)
Compatibility with other vaccines (multivalent vaccines or concomitant administration)
Production Amenability to large scale production
Cost of vaccine production and control
Delivery Quality of the supply chain
Cost of delivery systems
Acceptability by owners (Knowledgeacceptabilitypractices))
Competition with other control measures (antibiotics anti vector fight)
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments)
Specificities for the South andor for animals
Triggering a protective immune response
African swine fever
Need more
research
Modern adjuvants do not enhance the
efficacy of an inactivated African swine fever
virus vaccine preparation Blome S et al
Vaccine 2014
African Swine Fever Virus Georgia 2007 with
a Deletion of Virulence-Associated Gene 9GL
(B119L) when Administered at Low Doses
Leads to Virus Attenuation in Swine and
Induces an Effective Protection against
Homologous Challenge ODonnell V et al J
Virol 2015
Enhance the duration of immunity
CBPP
Mathematical modelling of the
transmission dynamics of
contagious bovine
pleuropneumonia reveals minimal
target profiles for improved
vaccines and diagnostic assays
Ssematimba A et al PLoS One 2015
Cheap existing vaccines
Not thermostable
Protection for 6 months (T1sr) to one year (T144)
Owners may prefer treating their animals with antibiotics
Target profile protection duration gt 2 years
bull Mutant library used to select one mutant in immuno-dominant antigen
bull Antibiotic selection marker removed + inactivation of antigen
bull Incorporation into water-in-oil emulsion preparation (Seppic)
bull increased thermostability
bull Laboratory trials in Bamako Mali good protection after 6 months
bull Adjuvant compatible with other vaccines Heartwater FMDhellip
Overcome protection failure Newcastle disease
Proteacuteine F aa 33-454 trimegravere
(a) Vu de la tecircte par le dessus
(b) Vu laterale
(a) (b)
All vaccines based on 50 year old strains
Did African strains derived
Wild and domestic bird surveillance in Africa
bull 13 000 samples
bull isolation and sequencing of 110 genomes
bull new genotypes amp phylogeographic study
bull divergences between these genotypes
and vaccine (14 substitutions in immunodominant areas)
Epitope mapping
Produce a cheap and ready to use vaccine
Heartwater
Perspectives
Cocktail of strains adapted regionaly for better cross protection
MAP1-related proteins
118+19+2025 3436384142675556
213743+44+45+46+6248+53T4SS
3551+52
Protein turnover processes
Chaperones
59274965
Proteinprocessing
and turnover
1757
Cell redox homeostatis
58+59 54
Amino acids
Fatty acids
Nucleotide
Pyrimidine
Purine
Pentose phosphate
GlycolysisTerpenoidSteroids
Glycerophospholipid
UbiquinoneHeme
SerGly PyruvateCysArg
Asp
Pro Gln
Glu
CofactorsCofactors
Glyoxylate
Folate (VitB9)
Oxidative phosphorylation
Orn
Lys
Tyr
Phe
63 268
4047
40
10
23
6+7
TCA cycle 4
24613
28+29+30+31
3322
Information processes
DNA Transcription
2 68
DNA replication
13+14 66
Translation
8 11 39 50+60
Hypothetical proteins
Back to fundamental studies Heartwater
Virulence mechanisms laquoomicsraquo bioinformatics amp functionnal studies
In vitro model for virulent amp attenuated strains
Transcriptomic amp proteomics of E ruminantium
SST4 effectors
1 Software SATE
2 Functionnal validation
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Impact assessment and research opportunities
Vaccine research
activities may be
based on expert
consultations
Priorities may vary
a lot between and
within a region
Expert review or
regional
workshops in
2002
Zoonotic diseases
New
vaccines
Modified
vaccines
Diagnostic Epidemiology Delivery
extension
1 Brucella abortus
2 Brucella melitensis
3 Trypanosomosis
4 Bovine tuberculosis
5 Leptospirosis
6 Anthrax
7 Cysticercosis
8 Buffalo pox
9 Rift Valley Fever
10 Toxocara vitulorum
11 Cysticercus bovis
12 Japanese B encephalitis
13 Schistosomosis
14 Botulism
15 Trichinella
16 Mange
17 Brucella suis
18 Rabies
19 Orf
What is needed for a vaccine
define research questions
Product Induction of solid immunity to re-infection
Duration of vaccinal immunityrequirement for administration of booster vaccinations
Safety
Thermostability
Markers to differenciate vaccinated from infected animals (DIVA)
Universality of protection (Antigenic variations in the pathogen)
Compatibility with other vaccines (multivalent vaccines or concomitant administration)
Production Amenability to large scale production
Cost of vaccine production and control
Delivery Quality of the supply chain
Cost of delivery systems
Acceptability by owners (Knowledgeacceptabilitypractices))
Competition with other control measures (antibiotics anti vector fight)
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments)
Specificities for the South andor for animals
Triggering a protective immune response
African swine fever
Need more
research
Modern adjuvants do not enhance the
efficacy of an inactivated African swine fever
virus vaccine preparation Blome S et al
Vaccine 2014
African Swine Fever Virus Georgia 2007 with
a Deletion of Virulence-Associated Gene 9GL
(B119L) when Administered at Low Doses
Leads to Virus Attenuation in Swine and
Induces an Effective Protection against
Homologous Challenge ODonnell V et al J
Virol 2015
Enhance the duration of immunity
CBPP
Mathematical modelling of the
transmission dynamics of
contagious bovine
pleuropneumonia reveals minimal
target profiles for improved
vaccines and diagnostic assays
Ssematimba A et al PLoS One 2015
Cheap existing vaccines
Not thermostable
Protection for 6 months (T1sr) to one year (T144)
Owners may prefer treating their animals with antibiotics
Target profile protection duration gt 2 years
bull Mutant library used to select one mutant in immuno-dominant antigen
bull Antibiotic selection marker removed + inactivation of antigen
bull Incorporation into water-in-oil emulsion preparation (Seppic)
bull increased thermostability
bull Laboratory trials in Bamako Mali good protection after 6 months
bull Adjuvant compatible with other vaccines Heartwater FMDhellip
Overcome protection failure Newcastle disease
Proteacuteine F aa 33-454 trimegravere
(a) Vu de la tecircte par le dessus
(b) Vu laterale
(a) (b)
All vaccines based on 50 year old strains
Did African strains derived
Wild and domestic bird surveillance in Africa
bull 13 000 samples
bull isolation and sequencing of 110 genomes
bull new genotypes amp phylogeographic study
bull divergences between these genotypes
and vaccine (14 substitutions in immunodominant areas)
Epitope mapping
Produce a cheap and ready to use vaccine
Heartwater
Perspectives
Cocktail of strains adapted regionaly for better cross protection
MAP1-related proteins
118+19+2025 3436384142675556
213743+44+45+46+6248+53T4SS
3551+52
Protein turnover processes
Chaperones
59274965
Proteinprocessing
and turnover
1757
Cell redox homeostatis
58+59 54
Amino acids
Fatty acids
Nucleotide
Pyrimidine
Purine
Pentose phosphate
GlycolysisTerpenoidSteroids
Glycerophospholipid
UbiquinoneHeme
SerGly PyruvateCysArg
Asp
Pro Gln
Glu
CofactorsCofactors
Glyoxylate
Folate (VitB9)
Oxidative phosphorylation
Orn
Lys
Tyr
Phe
63 268
4047
40
10
23
6+7
TCA cycle 4
24613
28+29+30+31
3322
Information processes
DNA Transcription
2 68
DNA replication
13+14 66
Translation
8 11 39 50+60
Hypothetical proteins
Back to fundamental studies Heartwater
Virulence mechanisms laquoomicsraquo bioinformatics amp functionnal studies
In vitro model for virulent amp attenuated strains
Transcriptomic amp proteomics of E ruminantium
SST4 effectors
1 Software SATE
2 Functionnal validation
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
What is needed for a vaccine
define research questions
Product Induction of solid immunity to re-infection
Duration of vaccinal immunityrequirement for administration of booster vaccinations
Safety
Thermostability
Markers to differenciate vaccinated from infected animals (DIVA)
Universality of protection (Antigenic variations in the pathogen)
Compatibility with other vaccines (multivalent vaccines or concomitant administration)
Production Amenability to large scale production
Cost of vaccine production and control
Delivery Quality of the supply chain
Cost of delivery systems
Acceptability by owners (Knowledgeacceptabilitypractices))
Competition with other control measures (antibiotics anti vector fight)
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments)
Specificities for the South andor for animals
Triggering a protective immune response
African swine fever
Need more
research
Modern adjuvants do not enhance the
efficacy of an inactivated African swine fever
virus vaccine preparation Blome S et al
Vaccine 2014
African Swine Fever Virus Georgia 2007 with
a Deletion of Virulence-Associated Gene 9GL
(B119L) when Administered at Low Doses
Leads to Virus Attenuation in Swine and
Induces an Effective Protection against
Homologous Challenge ODonnell V et al J
Virol 2015
Enhance the duration of immunity
CBPP
Mathematical modelling of the
transmission dynamics of
contagious bovine
pleuropneumonia reveals minimal
target profiles for improved
vaccines and diagnostic assays
Ssematimba A et al PLoS One 2015
Cheap existing vaccines
Not thermostable
Protection for 6 months (T1sr) to one year (T144)
Owners may prefer treating their animals with antibiotics
Target profile protection duration gt 2 years
bull Mutant library used to select one mutant in immuno-dominant antigen
bull Antibiotic selection marker removed + inactivation of antigen
bull Incorporation into water-in-oil emulsion preparation (Seppic)
bull increased thermostability
bull Laboratory trials in Bamako Mali good protection after 6 months
bull Adjuvant compatible with other vaccines Heartwater FMDhellip
Overcome protection failure Newcastle disease
Proteacuteine F aa 33-454 trimegravere
(a) Vu de la tecircte par le dessus
(b) Vu laterale
(a) (b)
All vaccines based on 50 year old strains
Did African strains derived
Wild and domestic bird surveillance in Africa
bull 13 000 samples
bull isolation and sequencing of 110 genomes
bull new genotypes amp phylogeographic study
bull divergences between these genotypes
and vaccine (14 substitutions in immunodominant areas)
Epitope mapping
Produce a cheap and ready to use vaccine
Heartwater
Perspectives
Cocktail of strains adapted regionaly for better cross protection
MAP1-related proteins
118+19+2025 3436384142675556
213743+44+45+46+6248+53T4SS
3551+52
Protein turnover processes
Chaperones
59274965
Proteinprocessing
and turnover
1757
Cell redox homeostatis
58+59 54
Amino acids
Fatty acids
Nucleotide
Pyrimidine
Purine
Pentose phosphate
GlycolysisTerpenoidSteroids
Glycerophospholipid
UbiquinoneHeme
SerGly PyruvateCysArg
Asp
Pro Gln
Glu
CofactorsCofactors
Glyoxylate
Folate (VitB9)
Oxidative phosphorylation
Orn
Lys
Tyr
Phe
63 268
4047
40
10
23
6+7
TCA cycle 4
24613
28+29+30+31
3322
Information processes
DNA Transcription
2 68
DNA replication
13+14 66
Translation
8 11 39 50+60
Hypothetical proteins
Back to fundamental studies Heartwater
Virulence mechanisms laquoomicsraquo bioinformatics amp functionnal studies
In vitro model for virulent amp attenuated strains
Transcriptomic amp proteomics of E ruminantium
SST4 effectors
1 Software SATE
2 Functionnal validation
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Triggering a protective immune response
African swine fever
Need more
research
Modern adjuvants do not enhance the
efficacy of an inactivated African swine fever
virus vaccine preparation Blome S et al
Vaccine 2014
African Swine Fever Virus Georgia 2007 with
a Deletion of Virulence-Associated Gene 9GL
(B119L) when Administered at Low Doses
Leads to Virus Attenuation in Swine and
Induces an Effective Protection against
Homologous Challenge ODonnell V et al J
Virol 2015
Enhance the duration of immunity
CBPP
Mathematical modelling of the
transmission dynamics of
contagious bovine
pleuropneumonia reveals minimal
target profiles for improved
vaccines and diagnostic assays
Ssematimba A et al PLoS One 2015
Cheap existing vaccines
Not thermostable
Protection for 6 months (T1sr) to one year (T144)
Owners may prefer treating their animals with antibiotics
Target profile protection duration gt 2 years
bull Mutant library used to select one mutant in immuno-dominant antigen
bull Antibiotic selection marker removed + inactivation of antigen
bull Incorporation into water-in-oil emulsion preparation (Seppic)
bull increased thermostability
bull Laboratory trials in Bamako Mali good protection after 6 months
bull Adjuvant compatible with other vaccines Heartwater FMDhellip
Overcome protection failure Newcastle disease
Proteacuteine F aa 33-454 trimegravere
(a) Vu de la tecircte par le dessus
(b) Vu laterale
(a) (b)
All vaccines based on 50 year old strains
Did African strains derived
Wild and domestic bird surveillance in Africa
bull 13 000 samples
bull isolation and sequencing of 110 genomes
bull new genotypes amp phylogeographic study
bull divergences between these genotypes
and vaccine (14 substitutions in immunodominant areas)
Epitope mapping
Produce a cheap and ready to use vaccine
Heartwater
Perspectives
Cocktail of strains adapted regionaly for better cross protection
MAP1-related proteins
118+19+2025 3436384142675556
213743+44+45+46+6248+53T4SS
3551+52
Protein turnover processes
Chaperones
59274965
Proteinprocessing
and turnover
1757
Cell redox homeostatis
58+59 54
Amino acids
Fatty acids
Nucleotide
Pyrimidine
Purine
Pentose phosphate
GlycolysisTerpenoidSteroids
Glycerophospholipid
UbiquinoneHeme
SerGly PyruvateCysArg
Asp
Pro Gln
Glu
CofactorsCofactors
Glyoxylate
Folate (VitB9)
Oxidative phosphorylation
Orn
Lys
Tyr
Phe
63 268
4047
40
10
23
6+7
TCA cycle 4
24613
28+29+30+31
3322
Information processes
DNA Transcription
2 68
DNA replication
13+14 66
Translation
8 11 39 50+60
Hypothetical proteins
Back to fundamental studies Heartwater
Virulence mechanisms laquoomicsraquo bioinformatics amp functionnal studies
In vitro model for virulent amp attenuated strains
Transcriptomic amp proteomics of E ruminantium
SST4 effectors
1 Software SATE
2 Functionnal validation
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Enhance the duration of immunity
CBPP
Mathematical modelling of the
transmission dynamics of
contagious bovine
pleuropneumonia reveals minimal
target profiles for improved
vaccines and diagnostic assays
Ssematimba A et al PLoS One 2015
Cheap existing vaccines
Not thermostable
Protection for 6 months (T1sr) to one year (T144)
Owners may prefer treating their animals with antibiotics
Target profile protection duration gt 2 years
bull Mutant library used to select one mutant in immuno-dominant antigen
bull Antibiotic selection marker removed + inactivation of antigen
bull Incorporation into water-in-oil emulsion preparation (Seppic)
bull increased thermostability
bull Laboratory trials in Bamako Mali good protection after 6 months
bull Adjuvant compatible with other vaccines Heartwater FMDhellip
Overcome protection failure Newcastle disease
Proteacuteine F aa 33-454 trimegravere
(a) Vu de la tecircte par le dessus
(b) Vu laterale
(a) (b)
All vaccines based on 50 year old strains
Did African strains derived
Wild and domestic bird surveillance in Africa
bull 13 000 samples
bull isolation and sequencing of 110 genomes
bull new genotypes amp phylogeographic study
bull divergences between these genotypes
and vaccine (14 substitutions in immunodominant areas)
Epitope mapping
Produce a cheap and ready to use vaccine
Heartwater
Perspectives
Cocktail of strains adapted regionaly for better cross protection
MAP1-related proteins
118+19+2025 3436384142675556
213743+44+45+46+6248+53T4SS
3551+52
Protein turnover processes
Chaperones
59274965
Proteinprocessing
and turnover
1757
Cell redox homeostatis
58+59 54
Amino acids
Fatty acids
Nucleotide
Pyrimidine
Purine
Pentose phosphate
GlycolysisTerpenoidSteroids
Glycerophospholipid
UbiquinoneHeme
SerGly PyruvateCysArg
Asp
Pro Gln
Glu
CofactorsCofactors
Glyoxylate
Folate (VitB9)
Oxidative phosphorylation
Orn
Lys
Tyr
Phe
63 268
4047
40
10
23
6+7
TCA cycle 4
24613
28+29+30+31
3322
Information processes
DNA Transcription
2 68
DNA replication
13+14 66
Translation
8 11 39 50+60
Hypothetical proteins
Back to fundamental studies Heartwater
Virulence mechanisms laquoomicsraquo bioinformatics amp functionnal studies
In vitro model for virulent amp attenuated strains
Transcriptomic amp proteomics of E ruminantium
SST4 effectors
1 Software SATE
2 Functionnal validation
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Overcome protection failure Newcastle disease
Proteacuteine F aa 33-454 trimegravere
(a) Vu de la tecircte par le dessus
(b) Vu laterale
(a) (b)
All vaccines based on 50 year old strains
Did African strains derived
Wild and domestic bird surveillance in Africa
bull 13 000 samples
bull isolation and sequencing of 110 genomes
bull new genotypes amp phylogeographic study
bull divergences between these genotypes
and vaccine (14 substitutions in immunodominant areas)
Epitope mapping
Produce a cheap and ready to use vaccine
Heartwater
Perspectives
Cocktail of strains adapted regionaly for better cross protection
MAP1-related proteins
118+19+2025 3436384142675556
213743+44+45+46+6248+53T4SS
3551+52
Protein turnover processes
Chaperones
59274965
Proteinprocessing
and turnover
1757
Cell redox homeostatis
58+59 54
Amino acids
Fatty acids
Nucleotide
Pyrimidine
Purine
Pentose phosphate
GlycolysisTerpenoidSteroids
Glycerophospholipid
UbiquinoneHeme
SerGly PyruvateCysArg
Asp
Pro Gln
Glu
CofactorsCofactors
Glyoxylate
Folate (VitB9)
Oxidative phosphorylation
Orn
Lys
Tyr
Phe
63 268
4047
40
10
23
6+7
TCA cycle 4
24613
28+29+30+31
3322
Information processes
DNA Transcription
2 68
DNA replication
13+14 66
Translation
8 11 39 50+60
Hypothetical proteins
Back to fundamental studies Heartwater
Virulence mechanisms laquoomicsraquo bioinformatics amp functionnal studies
In vitro model for virulent amp attenuated strains
Transcriptomic amp proteomics of E ruminantium
SST4 effectors
1 Software SATE
2 Functionnal validation
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Produce a cheap and ready to use vaccine
Heartwater
Perspectives
Cocktail of strains adapted regionaly for better cross protection
MAP1-related proteins
118+19+2025 3436384142675556
213743+44+45+46+6248+53T4SS
3551+52
Protein turnover processes
Chaperones
59274965
Proteinprocessing
and turnover
1757
Cell redox homeostatis
58+59 54
Amino acids
Fatty acids
Nucleotide
Pyrimidine
Purine
Pentose phosphate
GlycolysisTerpenoidSteroids
Glycerophospholipid
UbiquinoneHeme
SerGly PyruvateCysArg
Asp
Pro Gln
Glu
CofactorsCofactors
Glyoxylate
Folate (VitB9)
Oxidative phosphorylation
Orn
Lys
Tyr
Phe
63 268
4047
40
10
23
6+7
TCA cycle 4
24613
28+29+30+31
3322
Information processes
DNA Transcription
2 68
DNA replication
13+14 66
Translation
8 11 39 50+60
Hypothetical proteins
Back to fundamental studies Heartwater
Virulence mechanisms laquoomicsraquo bioinformatics amp functionnal studies
In vitro model for virulent amp attenuated strains
Transcriptomic amp proteomics of E ruminantium
SST4 effectors
1 Software SATE
2 Functionnal validation
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
MAP1-related proteins
118+19+2025 3436384142675556
213743+44+45+46+6248+53T4SS
3551+52
Protein turnover processes
Chaperones
59274965
Proteinprocessing
and turnover
1757
Cell redox homeostatis
58+59 54
Amino acids
Fatty acids
Nucleotide
Pyrimidine
Purine
Pentose phosphate
GlycolysisTerpenoidSteroids
Glycerophospholipid
UbiquinoneHeme
SerGly PyruvateCysArg
Asp
Pro Gln
Glu
CofactorsCofactors
Glyoxylate
Folate (VitB9)
Oxidative phosphorylation
Orn
Lys
Tyr
Phe
63 268
4047
40
10
23
6+7
TCA cycle 4
24613
28+29+30+31
3322
Information processes
DNA Transcription
2 68
DNA replication
13+14 66
Translation
8 11 39 50+60
Hypothetical proteins
Back to fundamental studies Heartwater
Virulence mechanisms laquoomicsraquo bioinformatics amp functionnal studies
In vitro model for virulent amp attenuated strains
Transcriptomic amp proteomics of E ruminantium
SST4 effectors
1 Software SATE
2 Functionnal validation
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Rift valley fever vaccines
The virus is endemic throughout much of the African continent However the
emergence of RVFV in the Middle East northern Egypt and the Comoros
Archipelago has highlighted that the geographical range of RVFV may be
increasing and has led to the concern that an incursion into Europe may
occur At present there is a limited range of veterinary vaccines available for
use in endemic areas and there is no licensed human vaccine
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Rift valley fever vaccines
Clone 13 (August 2010 South Africa amp Namibia)
bull Live naturally attenuated vaccine isolated from a benign human case
bull Easy and safe and cost effective production
bull Immunogenic after single dose
bull Long lasting immunity but recommend vaccination annually in endemic
areas
bull Safe for use in sheep goats and cattle
MP-12
bull Human isolate attenuated by serial passage in presence of a mutagen
bull Immunogenic safe in pregnant animals
bull DIVA possible
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Towards new RVF vaccines
Pox LSD or NDV vectors
bull expressing RVF Gn and Gc glycoproteins
Genetically modified vaccine from MP12
bull deletion of the NSs gene
bull mutant envelope protein
bull VLPs generated from the nucleoprotein and glycoproteins
Conclusion for RVF vaccines
bull Animal vaccines should be stockpiled in non-endemic areas
bull Urgent requirement for an approved human vaccine
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Disease eradication through vaccination PPR CBPP FA ND
Product Induction of solid immunity to re-infection -4 0 2 1
Duration of vaccinal immunityrequirement for administration of booster vaccinations -4 1 2 1
Safety 0 1 0 1
Thermostability 1 1 0 1
Markers to differenciate vaccinated from infected animals (DIVA) 1 0 0 1
Universality of protection (Antigenic variations in the pathogen) 0 0 2 0
Compatibility with other vaccines (multivalent vaccines or concomitant administration) 0 0 0 0
Production Amenability to large scale production 0 0 0 0
Cost of vaccine production and control 0 0 2 1
Delivery Quality of the supply chain 1 1 0 1
Cost of delivery systems 1 1 1 1
Acceptability by owners (Knowledgeacceptabilitypractices)) 0 1 2 1
Competition with other control measures (antibiotics anti vector fight) 0 1 0 0
Amenability to combine different tools in a global strategy (Slaughter antibiotic treatments) 2 0 2 2
Surveillance factors Typical clinical signs 0 1 0 1
Lab test for detection in live animals 0 0 0 0
Lab tests for detection in dead animals 0 0 0 0
DIVA tests 1 0 1 1
Rapid tests
Epidemiological factors Persitence in and multiplication in invertebrate vectors 0 0 0 0
Persistence in multiplication in the environment 0 0 2 0
Multiplicity of susceptible hosts 1 0 2 2
Importance of free living wildlife in maintenance of infection 1 0 4 4
Extent of pathogen antigenic variation (multiple serotypes or genetic drift) 0 0 1 1
Ability of recovered animals to transmit the infection 0 1 2 0
Level of immunity and duration for recovered vertebrates 0 0 1 0
Eradicability score 1 9 26 20
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Peste des Petits Ruminants global eradication
campaign Availability of highly efficacious single shot safe
and affordable (USD 01per dose) vaccines
Vaccines that can better withstand hotter climates
Producers of quality vaccines in Africa the Middle
East and Asia
Absence of a carrier state of any known reservoir of
the virus outside the domestic small ruminant
population
Availability of appropriate diagnostic tests and
protocols for surveillance
High-level commitment and compliance for PPR
vaccination expected from farmers
Growing political will from internationalregional
institutions and countries
Prediction An investment of USD 71 billion over 15 years
will eliminate the negative socio-economic
impact of PPR permanently and will result in
financial savings of USD 18 billion per year
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
PPR improved vaccine DIVA + thermostability
Development of a DIVA vaccine for the last stages of eradication
bull Reverse genetics tools immunogenic and specific epitope swap
bull Development of associated ELISA test (patent ndeg12 57980)
Capripoxvirus vectored recombinant vaccines
Vaccine vectors of choice
bull Safety
bull Thermostability
bull Large transgene insert capacity
bull Genetic stability
bull Specific tropism for Ruminants
T7 RNA Polymerase
PPRV genome N
P
L
Co-transfection
DIVA ring vaccination
Detection of infected animals
Slaughter of infected herdsanimals
Globulaire80 conserved TailHypervariable
N- -CNCORE NTAIL
0 400 525120 140
- +Vaccine mark
N - PPRV 75-1 vaccine
- +
Companion ELISAs
Pep E = PPRV 751
Pep 4 = marker
-+
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Implementation issues and economic studies
VacciCost A tool to estimate the
resource
requirements for
massive vaccination
campaigns
Cost of vaccine developement
Problem of private company involvement
Fied studies in endemic areas
Full cost to be considered and compared to other strategies
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Sociological studies
Participatory studies to develop vaccination strategies
bull Perception of disease and vaccination
bull Identification of socio-technic systems involved
bull Acceptability of control measures
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)
Conclusions
Vaccine development cannot be dissociated from control
strategies which define research questions
Specific constraints in the South and for animals
epidemiological studies production cost delivery DIVA
Need for integrated and multidisciplinary studies
microbiology vaccinology epidemiology economy
sociology
Huge work to be developped for PPR CBPP Newcastle
Heartwater RVFhellip
Combine vaccine development and control strategies for
zoonotic diseases (RVF)