ESSENTIAL PROTECTION

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1 ESSENTIAL PROTECTION for better life BROILER ND K VITABRON L VITAPEST L NEW L Supported by C H I C K P R O G R A M CONVENTIONAL vaccine range against Newcastle Disease CEVA HATCHERY I MMUNIZATION CONTROL KEYS

The disease and the context NEWCASTLE DISEASE: A PERMANENT THREAT > NEWCASTLE DISEASE (ND) is highly contagious, exists in a wide range of forms, and is one of the four major global poultry diseases.

The global impact of virulent ND is enormous.

In risky situations, health control programs and extensive vaccination is normally used to actively immunize chicks from as young as one day old.

Biosecurity > Although biosecurity plays an important role in preventing the spread of an ND virus, the disease can be transmitted through wind, birds, trucks, personnel and equipment.

2 The disease and the context NEWCASTLE DISEASE: A PERMANENT THREAT > NEWCASTLE DISEASE (ND) is highly contagious, exists in a wide range of forms, and is one of the four major global poultry diseases. It impacts all intensive poultry farming areas and spreads practically everywhere. Furthermore, it is one of the main barriers for international poultry product trade. The global impact of virulent ND is enormous. ND, caused by one serotype of Paramyxovirus, is still challenging veterinarians and farmers around the world despite the development of commercial, efficient vaccines over the past 8 years. In risky situations, health control programs and extensive vaccination is normally used to actively immunize chicks from as young as one day old. However, we must consider adapting the vaccination program to epidemiological and production situations. NEWCASTLE DISEASE: PREVENTION STRATEGY IN THE FIELD. Biosecurity > Although biosecurity plays an important role in preventing the spread of an ND virus, the disease can be transmitted through wind, birds, trucks, personnel and equipment. >Therefore, biosecurity rules are not always enough to prevent ND introduction and transmission in production facilities.. Vaccination > Very early vaccination is crucial to face early challenges. Prevention strategy For overall protection against Newcastle, Ceva Santé Animale offers a global range of vaccine solutions - Vectormune HVT NDV high-tech vectored vaccine and a conventional, non-vectored range: Cevac Broiler ND K, Cevac Vitabron L, Cevac Vitapest L and Cevac New L. > Hatchery spraying offers a unique opportunity to prime local immunity, followed by inactivated vaccine injection to achieve long-lasting protection.. live vaccines > ND virus strengths used in live vaccines can be divided into mesogenic, lentogenic and apathogenic strains according to pathogenicity. Immune response tends to increase as the pathogenicity of live vaccine increases, however, post-vaccinations reactions (PVR) increase proportionately. > Losses due to PVR continually threaten profitability for poultry operations.. Live + Inactivated Vaccines > Since the late 9s, the efficacy of using live plus inactivated vaccines to combat ND in hatcheries has been extensively demonstrated. > The combination induces protection and antibody levels significantly higher than those reached from the use of individual vaccines. % protection Age (days) Unvaccinated controls Live vaccine inactivated vaccine Live + inactivated vaccines >> Evolution of protection procured by live and inactivated vaccines administered individually or combined, to -day-old commercial chicks (Bennejean et al., 978). >> Newcastle Epidemiological situation. Database 9. Office international des épizooties OIE - Breeders vaccination programs consisting of both live and inactivated vaccines usually result in day-old chicks with high levels of maternal antibodies especially in high risk areas. While these antibodies are protective, they can also interfere with initial induction of humoral immunity. Although day-old chicks do not always uniformly respond with a raise in antibody titres because of maternal antibodies,, live plus inactivated vaccination at hatchery is extremely beneficial to prime local immunity in chickens. O O

ENHANCING local immunity with safe vaccines STRENGTHEN YOUR PROTECTION FROM THE FIRST DAY WITH A COMBINED VACCINATION PROGRAM > CEVAC VITAPEST L AND CEVAC VITABRON L The safest vaccines to

Ceva Santé Animale has extensively investigated the association of live and inactivated vaccines in hatcheries.

> Association of Cevac Vitapest L and Cevac Broiler ND K to induce protection against ND challenge: > CEVAC VITAPEST L: Contains the apathogenic PHY LMV strain.

> CEVAC VITABRON L: Safest combination of Newcastle + Infectious Bronchitis (IB) vaccine strains. Ready-to-use: no need to reconstitute two different vaccines.

protection AGAINST ND ( % ) 9 8 challenge ( weeks ) challenge ( weeks ) CEVAC broiler nd k cevac broiler nd k + cevac vitapest l CONTROL mean hi titre ( log ) 7 CEVAC broiler nd k age ( days ) cevac

3 ENHANCING local immunity with safe vaccines STRENGTHEN YOUR PROTECTION FROM THE FIRST DAY WITH A COMBINED VACCINATION PROGRAM > CEVAC VITAPEST L AND CEVAC VITABRON L The safest vaccines to effectively immunize day-old chicks against Newcastle and Newcastle+ Infectious Bronchitis. Stimulates early protection with minimal damage to trachea. Ceva Santé Animale has extensively investigated the association of live and inactivated vaccines in hatcheries. The combination of Cevac Vitapest L and Cevac Broiler ND K is proven to induce protection against ND challenge while minimizing PVR. > Association of Cevac Vitapest L and Cevac Broiler ND K to induce protection against ND challenge: > CEVAC VITAPEST L: Contains the apathogenic PHY LMV strain. Offers full protection against virulent Newcastle strains with better control of post-vaccination reaction (PVR). > CEVAC VITABRON L: Safest combination of Newcastle + Infectious Bronchitis (IB) vaccine strains. Ready-to-use: no need to reconstitute two different vaccines. Convenience: less storage space, easier ordering process. Lower risk of ND-IB interference: an apathogenic Newcastle strain is used. protection AGAINST ND ( % ) 9 8 challenge ( weeks ) challenge ( weeks ) CEVAC broiler nd k cevac broiler nd k + cevac vitapest l CONTROL mean hi titre ( log ) 7 CEVAC broiler nd k age ( days ) cevac broiler nd k + cevac vitapest l CONTROL CEVAC VITABRON L contains the apathogenic PHY.LMV. strain of ND, causing no tracheal lesions even to day-old chicks, and the Massachusetts H strain of IB. >> Comparison of protection (%) in a virulent ND challenge to commercial chickens at and weeks of age given by BROILER ND K alone and in combination with VITAPEST L applied at an day of age (Ceva, ). >> Mean HI titres observed after vaccination with BROILER ND K alone or in combination with Vitapest L in commercial chicks vaccinated at day of age (Ceva, ). Normal aspect (x) Severe congestion and lymphoid infiltration (x) C H I C K P R O G R A M >> Histology of trachea after vaccination with PHY. LMV.. SPF chicks, spray application (Ceva, ). >> Histology of trachea after vaccination with pneumotropic lentogenic ND vaccine strain. SPF chicks, spray application (Ceva, ). Ceva s high quality vaccines allows successful priming of day-old chickens from a single hatchery vaccination when applied properly. To ensure correct application, Ceva created the Ceva Hatchery Immunization Control Keys Program, or C.H.I.C.K. The C.H.I.C.K. Program guides you to better protection for your birds through specific attention to every stage of the vaccination process. O O

CEVAC BROILER ND K: HIGH ANTIGENIC CONCENTRATION REINFORCES PROTECTION Innovative formula combines high antigenic concentration with small volume (. ml).

> Comparative Immunogenicity test in sera collected and weeks after vaccination in SPF chickens. (Ceva, ) Haemagglutination inhibition (HI) titres to NDV were assayed.

Efficacy: high antigenic concentration TOLERAnce: perfectly tolerated at injection site birds were vaccinated with each vaccine and further chickens were kept as controls.

4 CEVAC BROILER ND K: HIGH ANTIGENIC CONCENTRATION REINFORCES PROTECTION Innovative formula combines high antigenic concentration with small volume (. ml). With the use of Binary Ethylene Imine (BEI) as an inactivation agent, Cevac Broiler ND K offers the best antigenic quality for better immune response. > Comparative Immunogenicity test in sera collected and weeks after vaccination in SPF chickens. (Ceva, ) Haemagglutination inhibition (HI) titres to NDV were assayed. Two week-old SPF chickens were immunized with / dose of the vaccines by SQ route. Efficacy: high antigenic concentration TOLERAnce: perfectly tolerated at injection site birds were vaccinated with each vaccine and further chickens were kept as controls. HI titre was determined using hemagglutinating units of antigen at and 8 days post vaccination. SAFETY: completely safe in young chicks Vaccine Vaccine A Vaccine B Vaccine C Cevac Broiler ND-K Sampling date D D8 D D8 D D8 D D8 Mean HI titre :8 :7 : : : : :8 : > Comparative efficacy test against virulent challenge at, 8 and days in commercial chicks. (Ceva, ) Sero positivity % % 7% 8% 9% 9% % % One-day old commercial chicks vaccinated with. ml IM inactivated vaccine. Challenge: EID of Herts strain,. ml by IM. weeks of monitoring. Serology monitoring in unchallenged birds. All chickens in the non-vaccinated control group remained sero-negative (log HI titre ). Immunogenicity of Cevac Broiler ND K batches tested over met the requirement (mean HI titre at least :). % protection Mean HI titre (log) 7 Vaccine competitor A induced comparable level of antibodies. Other competitor vaccines induced low level of antibodies and could not provide % seropositivity either or weeks post-vaccination when applied in reduced (/) dose. days 8 days days Broiler ND K C A Control B Age (days) Broiler ND K C A Control B B >>Comparison of the (%) protection procured by BROILER ND K and that of competitor vaccines (A, B, C) against virulent challenge at, 8 and days in commercial chicks (Ceva, ). >>Average of ND antibody titres after vaccination with BROILER ND K or competitor vaccines (A, B, C) in commercial chicks (Ceva, ). O O7

> Serological monitoring was performed after ND vaccination under field conditions of medium to high Newcastle pressure. ELISA and HI test were performed.

5 > Serological monitoring was performed after ND vaccination under field conditions of medium to high Newcastle pressure. ELISA and HI test were performed. (Lechuga, 9) 7, birds in a Million broiler farm reared in a medium-high ND pressure region. Marek HVT vaccine, SQ route at Day. Cevac Broiler ND K, SQ at Day. A Newcastle La Sota+Infectious Bronchitis vaccine, Eye drop at Day. FULL COMPATIBILITY WITH MAREK AND CEVAC TRANSMUNE IBD VACCINES > Compatibility study: Cevac Broiler ND K and cevac transmune IBD injected at one day by Desvac DOVAC double automatic machine. (Ceva, 7) Commercial broiler chickens (Ross 8) with maternal antibodies against Gumboro and ND were divided into groups. Compatibilty Cevac Vitapest, spray, at day. Full doses of Broiler ND K and /or Transmune IBD were injected. HI test result to ND : Mean (SD) day 7 days days days 8 days days days Log 8,8 9, 9,8 8,8 9 7,8 9,8 8, 9, 8, 8,. (.) n=. (.) n=. (.) n=. (.) n=. (.) n=.87 (.8) n=. (.7) n=,,8 Day days days 8 days days days 7, Broiler ND K Transmune IBD Broiler ND K & Transmune IBD Control IBDV SEROLOGICAL MONITORING BY VN (Virus neutralisation) The Biocheck Gumboro Elisa test performed on the same sera gave similar results to VN. All Transmune IBD vaccinated groups were positive by PCR at 8 and days. Titer Log,,,,,87, The combined vaccination of Cevac Broiler ND K and CEVAC Transmune IBD with the DOVAC double injector offers Gumboro protection comparable to vaccination with CEVAC Transmune IBD alone in timing and seroconversion level. > Compatibility study: Cevac Broiler ND K and Marek HVT- cell associated vaccine injected at day- old by Desvac DOVAC double automatic machine. (Ceva, 7) 7 8 Days of age Marek very virulent challenge (MDV RBB serotype virus) at days of age and weekly ND serological monitoring were performed. Commercial broiler chickens (Ross 8) with maternal antibodies against ND were divided in groups. Full dose of Broiler ND K and /or Marek vaccine were injected. Productive parameters in vaccinated chickens at the end of the cycle Housed Birds Livability Age to slaughter Weight (Kg) FCR Prod. Index 7, Groups Marek HVT vaccinated challenged birds Broiler ND K + Marek HVT vaccinated challenged birds Control no vaccinated challenged birds Number of birds Number of Marek positive birds Relative protection* (%) Marek PCR RBB serotype at 7 days Marek PCR HVT at 7 days % Positive Positive % Positive Positive 8 Positive Negative During the cycle, no evidences of a challenge by velogenic Newcastle, in terms of signs or lesions were detected. Serological and productive parameters were good according to the company standards. >> Marek disease challenge. *Levels of relative protection are acceptable considering a very virulent Marek experimental challenge. The combined vaccination of Cevac Broiler ND K and Marek HVT cell-associated vaccine with DOVAC double gives a similar protection against Marek challenge to the one achieved using a single HVT vaccine. O8 O9

Recommendation for use Low ND pressure light program / heavy ND pressure heavy program Combining live and inactivated vaccines against ND in day-old chicks strengthens and prolongs protection against

As ND pressure increases, using CEVAC VITAPEST L or CEVAC VITABRON (spray) and CEVAC BROILER ND K (subcutaneous injection) to immunize day-old chicks offers effective disease protection.

Conclusion In the field, the most important factors in preventing Newcastle Disease are possibly the environmental conditions and the effective practice of biosecurity.

Ceva works with you to offer the best protection against any Newcastle challenge, and offers a full range of vaccines and services for hatchery and field vaccination.

6 Recommendation for use Low ND pressure light program / heavy ND pressure heavy program Combining live and inactivated vaccines against ND in day-old chicks strengthens and prolongs protection against strong viral pressure. As ND pressure increases, using CEVAC VITAPEST L or CEVAC VITABRON (spray) and CEVAC BROILER ND K (subcutaneous injection) to immunize day-old chicks offers effective disease protection. Revaccination against ND at farms may be necessary depending on field conditions. Conclusion In the field, the most important factors in preventing Newcastle Disease are possibly the environmental conditions and the effective practice of biosecurity. Newcastle vaccination dates and types must be proposed according to local epidemiological situations. Ceva works with you to offer the best protection against any Newcastle challenge, and offers a full range of vaccines and services for hatchery and field vaccination. Conclusion > Booster in farms Spraying is the only technique to ensure the best immunity, and is strongly advised over using the drinking water technique. CEVAC VITAPEST L and CEVAC VITABRON L must be administered by spraying. > HIGH NEWCASTLE PRESSURE: BOOST IN FARMS WITH LA SOTA STRAIN Despite the highest residual pathogenicity, lentogenic strains like La Sota are strongly immunogenic and widely used all over the world especially in endemic areas as a booster vaccination. As lentogenic strain, it has greater spreading potential than other strains and it may be applied by Drinking water route. > CEVAC NEW L Live attenuated La Sota strain vaccine. Recommended for booster vaccination in cases of high Newcastle pressure. References. Alexander, D.J and Jones, R.C.. Newcastle Disease, Other Avian Paramyxovirus, and Pneumovirus Infections. In:Y.M. Saif (Ed.) Diseases of Poultry, th Edition, p. -9. Iowa State Press.. Al-Garib, S.O., Gielkens, A.L.J., Gruys, E. and Koch,G.. Review of Newcastle disease virus with particular references to immunity and vaccination. World s Poultry Science Journal, V. 9, p Bennejean, G., Guittet, M., Picault, J.P., Bouquet, J.F., Devaux, B., Gaudry, D. Moreau, Y Vaccination of day-oldchicks against Newcastle Disease using inactivated oil adjuvant vaccine and/or live vaccine. Avian Pathology, v. 7, n.,p Buonavoglia C et al 988 Veterinary Research Communications,, -: CEVA Santé Animale,.CEVA-Phylaxia. Study Report. No.DV--.. CEVA Santé Animale, 7. CEVA-Phylaxia. Study Reports No DV-8-7 and DV CEVA Santé Animale,. CEVA-Phylaxia. Study Report. No.D-. 8. Eidson, C.S. Thayer, S.G., Villegas, P., Kleven, S.H. 98. Vaccination of Broiler Chicks from Breeder Flocks Immunized with a Live or Inactivated Oil Emulsion Newcastle Disease Vaccine. Poultry Science, v., p Giambrone, J.J. 98. Laboratory Evaluation of Newcastle Disease Vaccination Programs for Broiler Chicks. Avian Diseases, v. 9, p Giambrone, J.J. and Closser, J. 99. Effect of Breeder Vaccination on Immunization of Progeny against Newcastle Disease. Avian Diseases, v., p Lechuga M. 9. Ceva Mexico. Study report N9.. Office International Des Epizooties (OIE).. Newcastle Disease. In: Manual of Standards Diagnostic Tests andvaccines, th Edition.. Paniago Marcelo.. Newcastle Disease Prevention. Ceva Animal Health Asia Pacific.. Partadiredja, M., Eidson, C.S., Kleven, S.H A Comparison of Immune Responses of Broiler Chickens to Different Methods of Vaccination Against Newcastle Disease, Avian Diseases v., n., p. -.

7 C H I C K P R O G R A M Efficient hatchery vaccination offers consistent protection and better control. To achieve the best results, the Ceva range of Newcastle vaccinations for hatchery application is supported by the C.H.I.C.K. Program BROILER ND K >Inactivated emulsion vaccine against Newcastle Disease, La Sota strain. >Specifically designed for young chicks. ml / dose >High antigenic concentration. >Optimum tolerance through improved fluidity and reduced volume of injection. > Strong and long-lasting enhancement of ND immunity through synergy with a live vaccine: CEVAC Vitapest L. VITABRON L > Live attenuated combined vaccine, Phy LMV., strain of Newcastle Disease and Massachusetts serotype, H strain of Infectious Bronchitis. > The safest combination of Infectious Bronchitis (IB) and Newcastle Disease (ND) vaccines for spray application. > The best control of IB-ND interference, using a respiratory strain (H) and an apathogenic strain (Phy.lmv.). VITAPEST L >Live attenuated vaccine against Newcastle Disease, Phy.LMV. strain. >Enterotropic apathogenic vaccine (ICPI-), no post-vaccination reaction. > Full and quick protection against virulent strains of Newcastle Disease, after spray application. NEW L >Live attenuated vaccine La Sota strain. >Lentogenic strain widely used all over the world. > Recommended for booster vaccination by eye-drop or drinking water administration in cases of high Newcastle pressure. CEVA SANTE ANIMALE, Avenue de la Ballastière - BP - LIBOURNE Cedex (France) Tel : Fax :

CEVAC CEVAC BROILER ND K / 5000 doses

CEVAC CEVAC BROILER ND K / 5000 doses CEVAC BROILER ND K / 5 doses CEVAC BROILER ND K Newcastle disease a permanent threat Newcastle Disease is highly contagious and exists in a wide range of forms. It is one of the four major poultry diseases