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Défis Scientifiques et Economiques du Développement de Vaccins pour les Pays du Sud: maladies animales et zoonotiques Thierry Lefrançois, François Thiaucourt, Renaud Lancelot UMR Cirad-Inra CMAEE « Contrôle des maladies animales exotiques et émergentes » 2 décembre 2015

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Page 1: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 2: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 3: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 4: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 5: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 6: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 7: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 8: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 9: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 10: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 11: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 12: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 13: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 14: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 15: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 16: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 17: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 18: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)

Page 19: Défis Scientifiques et Economiques du Développement de Vaccins …corevac.org/sites/default/files/public/fichiers_attaches/thierry... · Défis Scientifiques et Economiques du Développement

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)