Les Vaccines Anti-Brucelliques. Dakar, 16 Juin 2015

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1 Les Vaccines Anti-Brucelliques Dakar, 16 Juin 2015

2 Agenda CZ Veterinaria Brucella vaccines Vaccination strategies

3 Products Solutions Travaillant à la prévention de maladies pour un monde plus salutaire

4 Que faisons-nous Leader mondialen découverte, développement, fabrication et commercialisation de vaccins de santé animale. 152 personnesayant leur siège à Vigo (Espagne), y compris 12 scientifiques et spécialistes vétérinaires de R&D. 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 choisipar 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.

5 Principaux Vaccins pour les Licitations Publiques ETADEX (Rage, inactivé) B-19 CZV (Brucelle, vivant atténué RB-51 CZV (Brucelle, vivant atténué) REV-1 (Brucelle, vivant atténué) OCUREV (Brucelle, vivant atténué) Principaux Diagnostiques pour les Licitations Publiques ROSE BENGALE TUBERCULINE AVIAIRE TUBERCULINE BOVINE

6 CZV "Sucess Stories". Brucella First company in developingthe conjunctivaladministration. 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 Cooperation with Official Veterinary Services in 35 countries Annual Production Capacity: 120 M doses

7 Brucellavaccines

8 OIE recommended Brucella vaccines B. abortus: S19 and RB51 B. melitensis: Rev-1 Efficacious Stable (international standards) Live attenuated, smooth strain of B. abortus. Freeze-dried vaccine with diluent Subcutaneous route(sc) and Conjunctival route(co) Long-lasting protection due to CMI (cell mediated immunity)

9 OIE recommended Brucella vaccines BUT Originally designed to vaccinate young animals (3-6 months) Diagnostic interferences that could be avoided (RB51 and conjunctival administration) Abortion in pregnant females. Milk excretion when used in pregnant cows. Rare but possible Causes testicular alterations when vaccinating males Safety concerns: animals and humans

10 Other vaccines/strains B. abortus:45-20, 104 M B. melitensis: M111, H38 China: A19, M5 and S2 Russia.-22 strains from

11 Public Health impact Prevention of animal brucellosis VACCINATION Prevention of human brucellosis 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

12 Public health impact: Human cases Year 1994= 1243 cases Year 2008= 56 cases Year 1991 = 3000 cases Year 2006 = 200 cases Year 2011 =103 cases Year 2012 = 85 cases

13 Ideal Brucellavaccine: TPP Efficacy: > 80-85% protecion DOI: Long-lasting protection Safety: no adverse reactions Not causing infection to humans Thermostable DIVA vaccines Cross-protection Low-cost

14 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 RB51 Rough attenuated vaccine DIVA vaccines Protection only against Brucella abortus Final steps of Eradication

15 RB51 S19

16 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 Protection conferred is similar Different Serological response Fewer abortions compared to SC

17 Conjunctivalvaccination NINETIES: Rev-1 SC (1-2x10 9 UFC/ dose) SUSTITUTION Rev-1 Conjunctival (1-2x10 9 UFC/ dose) Compatible with Test and Slaughter Good level of protection: Cell mediated immune response Safer than Rev-1 SC. Mass vaccination estrategy

18 Conjunctivalvaccination Vaccination of replacement flocks. (% of positive animals after vaccination) It causes problems for the application of test and slaughter programmes. Weak and short-lasting serological response which avoids interference with serological tests. IMMUNE RESPONSE Long lasting serological response: Antibody response is not important. Cell mediated immunity is the most important protection. (Plommety Fensterbank1976. Ann RechVét7, 9; Díaz et al J Clin Microbiol10, 37; Alonso et al 1988 J Clin Microbiol, 26, 2642 ; Nielsen and Gall J Immun Immunochem. 22:183; Muñoz et al 2005,

19 Interferencewithdiagnosis Scapular L.N. Cranial L.N

20 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. Choosing a proper vaccination route is essential to immunize the animals. BUT Vaccinating animals by conjunctival route may be difficult in some cases.

21 Vaccination strategies

22 Defining the program Diagnostics and Official Laboratories Official Veterinary Services. Organization Animal Identification and animal movement control Epidemiological survey: Prevalence Compensation T+S Compulsory vs. Optional Vaccine Quality Control. Vaccination coverage Training, awareness and involvement (farmers, vets ) BUDGET & COMMITMENT

23 FINAL GOAL = ERADICATION FIRST STEP = CONTROL Vaccination Strategies

24 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 100% of the flocks Individual identification (recommendable, but not essential) Disadvantages: Extensive/nomadic systems Continued reproduction (not seasonal) Vaccination coverage

25 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 Identify the ideal season/period for vaccination (avoid side effects) BEST alternativein endemicareas with high prevalence and uncontrolled flocks

26 Strategies: Mass +Replacement vaccination Initial mass vaccination in combination with vaccination of replacement animals in subsequent years 1 st year: individual identification and vaccination of 100% of the animals (in the ideal period) Following years: vaccination and exclusive identification of the Following years: vaccination and exclusive identification of the non-identified animals (normally young replacement animals)

27 Eradication program in Spain

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30 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 Europe: RB51 and Rev-1 CO MENA: Rev-1, S19, RB51 S19 conjunctival: Turkey, Tunisia

31 Control vs Eradication CO route is safer than SC Conclusions Available vaccines are good enough for tackling brucellosis High Quality vaccines (efficacy, stability ) Mass vaccination every 2-3 years is the best strategy T+S are expensive and unsustainable where prevalence is high 5 to 10 years strategy THERE IS NO STANDARD STRATEGY

32 THANK YOU