Les Vaccines Anti-Brucelliques

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Dakar, 16 Juin 2015

Agenda

• CZ Veterinaria

• Brucella vaccines

• Vaccination strategies

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Products Solutions

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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

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THANK YOU

p.rey@czveterinaria.com