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Les Vaccines Anti-Brucelliques
CONFIDENTIAL
Dakar, 16 Juin 2015
Agenda
• CZ Veterinaria
• Brucella vaccines
• Vaccination strategies
CONFIDENTIAL
Products Solutions
CONFIDENTIAL
Travaillant à la prévention de maladies pour un monde plus salutaire
Que faisons-nous
• Leader mondial en découverte, développement, fabrication et
commercialisation de vaccins de santé animale.
• 152 personnes ayant leur siège à Vigo (Espagne), y compris
12 scientifiques et spécialistes vétérinaires de R&D.
• Un portefeuille varié de produits vétérinaires (et de services
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• Un portefeuille varié de produits vétérinaires (et de services
de Contract Manufacturing et d´enregistrement de dossiers)
pour les animaux d´élevage et les animaux de compagnie.
• Partenaire choisi par les vingt principales entreprises
pharmaceutiques, preuve de la qualité supérieure de nos
produits et nos services.
• Nous opérons dans plus de 80 pays du monde entier.
Principaux Vaccins pour les Licitations Publiques
ETADEX®
(Rage,
inactivé)
OCUREV®
(Brucelle, vivant
atténué)
REV-1®
(Brucelle, vivant
atténué)
RB-51 CZV®
(Brucelle, vivant
atténué)
B-19 CZV®
(Brucelle, vivant
atténué
Principaux Diagnostiques pour les Licitations
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Principaux Diagnostiques pour les Licitations
Publiques
ROSE
BENGALE® TUBERCULINE AVIAIRE® TUBERCULINE BOVINE®
CZV "Sucess Stories ". Brucella
• First company in developing the conjunctival administration.
• Improvement of vaccine’s stability (up to 3 years shelf life)
• R&D of new generation Brucella vaccines
• Wide range of products: OIE recommended vaccines
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• Wide range of products: OIE recommended vaccines
• Cooperation with Official Veterinary Services in 35 countries
• Annual Production Capacity: 120 M doses
Brucella vaccines
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OIE recommended Brucella vaccines
• B. abortus: S19 and RB51
• B. melitensis: Rev-1
• Efficacious
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• Stable (international standards)
• Live attenuated, smooth and rough strains. Freeze-dried vaccine with diluent
• Subcutaneous route (SC) and Conjunctival route (CO)
• Long-lasting protection due to CMI (cell mediated immunity)
OIE recommended Brucella vaccines
BUT…
• Originally designed to vaccinate young animals (3-6 months)
• Diagnostic interferences that could be avoided (RB51 and
conjunctival administration)
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• Abortion in pregnant females.
• Milk excretion when used in pregnant animals
• Causes testicular alterations when vaccinating males
• Safety concerns: animals and humans
Other vaccines/strains
• B. abortus:45-20, 104 M
• B. melitensis: M111, H38, B115
• China: A19, M5 and S2
• Russia.- 22 strains from 1922-1997.
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Public Health impact
Prevention of animal brucellosis
Prevention of human brucellosis
VACCINATION
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The best method for prevention and control
The first step on the way to control de disease
The only practical and economical method of control
Public health impact: Human cases
Year 1994= 1243 cases
Year 2008= 56 cases
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Year 1991 = 3000 cases
Year 2006 = 200 cases
Year 2011 =103 cases
Year 2012 = 85 cases
Ideal Brucella vaccine: TPP
• Efficacy: > 80-85% protecion
• DOI: Long-lasting protection
• Safety: no adverse reactions
• Not causing infection to humans
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• Not causing infection to humans
• Thermostable
• DIVA vaccines
• Cross-protection
• Low-cost
Brucella abortus: RB51 vs. S19
• S19
– Smooth attenuated strain
– S19 by subcutaneous route (SC) is one of the most widely used vaccine
– Very good protection
– Cross protection against Brucella melitensis in cattle has been demonstrated
– Control � S19 CO for Eradication
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– Control � S19 CO for Eradication
• RB51
– Rough attenuated vaccine
– DIVA vaccine
– Protection only against Brucella abortus
– Final steps of Eradication
S19
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RB51
B. melitensis Rev-1 strain
• Rev-1 is an attenuated, smooth strain of B. melitensis.
• It is the most widely used vaccine.
• It is the most effective vaccine available.
Ocurev vs. CZV Rev-1
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Ocurev vs. CZV Rev-1– Protection conferred is similar
– Different Serological response
– Fewer abortions compared to SC
Conjunctival vaccination
Rev-1 SC
(1-2x109 UFC/ dose)
Rev-1 Conjunctival
(1-2x109 UFC/ dose)
NINETIES: 1990-2000
SUSTITUTION
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Compatible with Test and Slaughter
Good level of protection: Cell mediated immune response
Safer than Rev-1 SC.
Mass vaccination estrategy
Conjunctival vaccinationVaccination of replacement flocks. (% of positive animals after vaccination)
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IMMUNE RESPONSE
Long lasting serological response: Antibody response is not important.
Cell mediated immunity is the most important protection.
It causes problems for the application
of test and slaughter programmes.
Weak and short-lasting serological
response which avoids interference
with serological tests.
(Plommet y Fensterbank 1976. Ann Rech Vét 7, 9; Díaz et al 1979. J Clin Microbiol 10, 37; Alonso et al 1988
J Clin Microbiol, 26, 2642 ; Nielsen and Gall. 2001. J Immun Immunochem. 22:183; Muñoz et al 2005,
Interference with diagnosis
Scapular L.N.
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Cranial L.N
Disemination. Justifying the CO route
• Conjunctival, Oral and Nasal are the entry routes.
• Cranial lymph nodes are the ideal location for Brucella’s
replication.
• Stablishing immunity at the entry point seems the best
strategy.
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strategy.
• Choosing a proper vaccination route is essential to immunize
the animals.
BUT
• Vaccinating animals by conjunctival route may be difficult in
some cases.
Vaccination strategies
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Defining the program
• Diagnostics and Official Laboratories
• Official Veterinary Services. Organization
• Animal Identification and animal movement control
• Epidemiological survey: Prevalence
• Compensation � T+S
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• Compensation � T+S
• Compulsory vs. Optional
• Vaccine Quality Control. Vaccination coverage
• Training, awareness and involvement (farmers, vets…)
BUDGET & COMMITMENT
Vaccination Strategies
• FINAL GOAL = ERADICATION
• FIRST STEP = CONTROL
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Strategies: Replacement vaccination
• Exclusive vaccination of replacement animals (3 – 4 months)
every year
• Yearly rate of replacement = 20% → 100% of the population
vaccinated every 5 years.
• It is necessary to vaccinate 100% of the target animals and
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• It is necessary to vaccinate 100% of the target animals and
100% of the flocks
• Individual identification (recommendable, but not essential)
• Disadvantages:
– Extensive/nomadic systems
– Continued reproduction (not seasonal)
– Vaccination coverage
Strategies: Mass vaccination
• Vaccination of adults
• Massive vaccination every X years (i.e. 2 years)
• Annual replacement rate = 20% → in 2 years 40% of the
population has been vaccinated.
• Animal Identification
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• Animal Identification
• Identify the ideal season/period for vaccination (avoid side
effects)
BEST alternative in endemic areas with
high prevalence and uncontrolled flocks
Strategies: Mass +Replacement vaccination
• Initial mass vaccination in combination with vaccination of
replacement animals in subsequent years
• 1st year: individual identification and vaccination of 100% of
the animals (in the ideal period)
• Following years: vaccination and exclusive identification of the
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• Following years: vaccination and exclusive identification of the
non-identified animals (normally young replacement animals)
Eradication program in Spain
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Strategies by region
• China: A19, M5 and S2
• Russia.- Rev-1, S19 and S82
• CIS Region.- Rev-1 and S19
• Latam: S19+RB51. Rev-1 is not significant
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• Europe: RB51 and Rev-1 CO
• MENA: Rev-1, S19, RB51
• S19 conjunctival: Turkey, Tunisia…
Conclusions
• Control vs Eradication
• CO route is safer than SC
• Available vaccines are good enough for tackling brucellosis
• High Quality vaccines (efficacy, stability…)
• Mass vaccination every 2-3 years is the best strategy
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• Mass vaccination every 2-3 years is the best strategy
• T+S is expensive and unsustainable where prevalence is high
• 5 to 10 years strategy
THERE IS NO STANDARD STRATEGY