Ceva s offer to optimize performance Simpler vaccination and better safety

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1 Ceva s offer to optimize performance Simpler vaccination and better safety Rick van Oort Poultry Corporate Range Manager Layer range CEVA Sante Animale Bangkok-Thailand March 12, 2013

Bodyweight (g) 1600 1550 1500 1450 1400 1350 1300 1250 1200 1150 1100 1050 1000 950 900 850 800

skeleton/immunnesystem formation Rearing period 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Age

2 Bodyweight (g) Breed recommendations First 5 wks skeleton/immunnesystem formation Rearing period Age in weeks Uniformity is crucial Bodyweight development during start of production!!! Target bodyweight 2

3 Essential: Feed, Water & Management Disease protection 3

Bodyweight (g) Consequences on the QUALITY of

1350 1300 1250 1200 1150 1100 1050 1000 950

350 300 250 200 150 100 50 0 Premium Quality

17 Age in weeks MEDIUM OR BAD QUALITY Lower

5 Bodyweight (g) Consequences on the QUALITY of PULLETS before onset of lay Premium Quality PULLET Age in weeks MEDIUM OR BAD QUALITY Lower Bodyweight Bad uniformity Target bodyweight Actual bodyweight

6 Ambitions of Ceva Develop vaccines which are easier applied (mass application & hatchery application) and provide long duration of immunity Vector vaccines Develop broad viral & bacterial combi vaccines to reduce stress impact on birds Broad combination vaccines Develop tools for easier bird & operator friendly application Specialized vaccination equipment CHICK & EGGS program service to assist in preparation, and application of the vaccine

7 Layer/breeder Hatchery vaccination

8 SPF layers Efficacy Cevac MD Rispens (trial set up) Day old vaccination, sub-q route Challenge strain (RB1B strain) 0,2 ml injected S.Q in the neck, 5 days post vaccination Group Treatment Vaccination age Challenge Observation period 1 Cevac MD Rispens (in-ovo) 18 Days 5 days old Until 50 days of age 2 Cevac MD Rispens (s.c) 3 Com HVT (sq) 4 Neg. control Day old 5 days old Until 50 days of age Day old 5 days old Until 50 days of age NA NA Until 50 days of age 5 Pos. Control NA 5 days old Until 50 days of age

9 100% Protection of Cevac MD Rispens against very virulent Marek s disease 95% 98% 90% 80% 70% 68% 60% 50% 40% 30% 20% 10% 5% 0% Cevac MD Rispens (s.q route) Cevac MD Rispens (in-ovo route) HVT (s.q) Positive control

10 Vaccinated at day old (s.c) Shedder trial results (internal trial) Ceva MD Rispens & control group Challenge day old of shedder groups (very virulent + MD strain 648 A and placing together with vaccinated groups Mortality and Marek s lesions evaluation were followed for 18 weeks.

11 80% Protection Index (PI) against very virulent + Marek s Disease Shedder trial challenge 60% 40% 68% 20% 20% 0% Cevac Rispens HVT FD No vaccine 0%

12 Conclusion Cevac MD Rispens provides strong marek protection against very virulent + marek disease virus, compared to groups receiving only HVT or no vaccine

13 Duration of immunity in Layers

14 Duration of immunity in layers Commercial brown pullets with different vaccination schedules Regular challenge from 3 weeks to 72 weeks of age. Challenge strain two genetically heterologous genotype VII NDV strains. Insert in vaccine is Genotype I strain Follow up of protection, shedding.

Challenge strains To test the onset and duration of immunity of Vectormune ND (insert: genotype I) in commercial layers against two genetically heterologous genotype

02 SG-4H/65 ZA-5/68 D1608/2/2/11MY D1543/9/1/410MY D1524/1/2/10MY D1445/1/09ID MB128/04 W3/89ID 904/87 ID DI-3/88 DE-85/96 NL-2/93 DE-82/94 MB064/05 NDV08-022

1083/72USA Israel 70 Iraq AG68 H-310/82 DK-1/95 4100/99MX 5166/98MX 229808/03US 456/04MX 466/06MX D516/1/09MX D1112/09MX D1633/3/1/11MX D1559/8/10MX ZA-18/90 ZA-16/90

15 Challenge strains To test the onset and duration of immunity of Vectormune ND (insert: genotype I) in commercial layers against two genetically heterologous genotype VII NDV strains. Distance 0.02 SG-4H/65 ZA-5/68 D1608/2/2/11MY D1543/9/1/410MY D1524/1/2/10MY D1445/1/09ID MB128/04 W3/89ID 904/87 ID DI-3/88 DE-85/96 NL-2/93 DE-82/94 MB064/05 NDV JS/10/05/CN GMPV171/06ZA ZA378/F/00 ZA308/B/99 Taiwan95 MB076/05 DE-372/86 P/avian/Peru/ /08 D575/6/05PE pide-68/94 pide2653/9 pi17498/98 Warwick /72USA Israel 70 Iraq AG68 H-310/82 DK-1/ /99MX 5166/98MX /03US 456/04MX 466/06MX D516/1/09MX D1112/09MX D1633/3/1/11MX D1559/8/10MX ZA-18/90 ZA-16/90 Miyadera/51 AU Victoria/32 Italien45 Herts33 V4Queensland/66 D26-76 I-2 Vitapest Ulster2C67 TexasGB/48 BeaudetteC/45 LaSota/46 clone_30 B1_ Genotype VIIa Genotype VI Genotype VIII Genotype VII? Genotype VIId Genotype V Genotype III Genotype IV Genotype I Genotype II Challenge strains Genotype VIIb Vaccine insert 16

16 Clinical protection (MY) Onset and duration At 3 weeks of age already significant (~75%) protection was seen which reached almost complete (95%) protection by 4 weeks of age regardless the vaccination programs. 100 % clinical protectection was achieved from 6 to 72 weeks of age.

17 Challenge at 33 weeks of age Egg production Clinical protection: 100% 100% NA (unvaccinatedchallenged controls: 0%) NB: negative control group was transported and mock challenged to mimic all stress factors. A.d.=acclimatization day; dpch=days post-challenge No significant effect of challenge could be detected on vaccinated hens!

18 Conclusion Vectormune ND is able : To induce long lasting protection To control mortality when birds face ND challenge To better control the egg drop production To better control NDV virus shedding

19 Better Organization, Better Ergonomy, Better QUALITY in Hatchery vaccination

20 Field vaccination Subcutaneous Wing Web Spray Intramuscular Drinking Water Eye-drop

21 Warming up of the vaccines (bacterial) Water bath: 40 o 42 o C

23 Poor Injection quality (too deep injection) 24

24 Poor Injection quality

25 % of flocks Proper injection? Post-mortem examinations of 1486 flocks of pullets (5 pullets / flock ; weeks; France) ,5 7, N of pullets with trace of injection After R. Doucet and G. Guyony, 1997 Conclusion: 30% of flocks were not correctly vaccinated!

26 Machine developed for quality I.M breast injections For IM breast injection of layers and breeders 3 Detection points assure precision and safety of injection Precise injection side angle and depth Is not a speed accelerator 27

Avoids hitting clavicles Eliminates risk of injecting

27 Quality injection Injection in the place where most muscle tissue is present Avoids hitting breast bone Avoids hitting clavicles Eliminates risk of injecting too low Constant injection depth Limits the risk of self injection 28

were compared 18 WEEKS 21 WEEKS 26 WEEKS BW (g) % Unif BW (g) % Unif BW (g) % Unif IM INJECTOR

28 Field Trial Two flocks were vaccinated with Cevac ND IB EDS K at 18 weeks One was vaccinated with manual syringe One was vaccinated with IMVAC (Automatic IM Injector) Bodyweight and titers were compared 18 WEEKS 21 WEEKS 26 WEEKS BW (g) % Unif BW (g) % Unif BW (g) % Unif IM INJECTOR 1,632 70% 1,794 75% 1,888 85% MANUAL SERYNGE 1,611 70% 1,676 65% 1,820 85% STANDART 1,550 1,705 1,830

29 Better Organization, Better Ergonomy, Better QUALITY in Field vaccination

30 Innovation in products Marek vaccines Cevac MD Rispens Cevac MD HVT & Rispens Vector vaccines Vector HVT vaccines Vectormune ND & Vectormune ND + Rispens Vectormune IBD & Vectormune IBD + Rispens Vectormune LT Vectormune -AI Vector FP vaccines Vectormune FP-LT (+AE)) Vectomune FP-MG (+AE) Broad combination inactivated vaccines Cevac Corymune range Cevac Corymune 4K Coryza + Salmonella Cevac Corymune 7K Coryza + Salmonella + ND + IB +EDS No extra vaccinations needed for salmonella control

32 Trial Details Location : Asia Number of birds: 20,000 Intake date: 8 th & 9 th July 2011 End of trial: October 2012 Intake Group No. of birds (intake) MG Treatment Program 8 th July 11 Flock 1 9,457 Tylosin 9 th July 11 Flock 2 9,457 Vectormune FP - MG

33 Farm Vaccination Program Age Vaccination Route D1 ND + IB Live Spray D4 Cocci DW D9 ND Live Spray D12 IB Live Spray D14 IBD Live DW D18 21 ND + IB Live ND Killed Vectormune FP-MG D25 IBD Live DW 6 wks Reo Live SQ D55 ND ( La Sota) + IB (Mass) Live DW 10 wks ND + IB Live DW DW IM 0.5 ml Wing Web 11 wks Fowl Pox + AE + CAV Wing web 12 wks Coryza IM 14 wks ND + IB Live DW 16 wks ND + IB + EDS + Coryza IM 19 wks ND La Sota ND IB IBD Reo 22, 32, 40, 48, 56, 64 wks ND + IB Live DW 26, 36, 44, 52, 60 wks ND live Spray ED IM

34 MG ELISA (Mean) Titer - IDEXX Positive level >1,100 unit Based on Mean titer, at wk 55, Tylosin and VTM FP-MG group turned positive with 1,197 and 1,205 ELISA unit respectively.

35 Overall Egg Production % MG positive Elisa No drop in egg production No clinical MG signs Until 62 wks Standard VTM FP MG group Tylosin group DIFF (VTM Tylosin) Average Egg Production % 64.7% 64.5% 60% +4.5% Total Egg HH

36 Suspected age where flock may infected with MG (based on MG serology) PCR Result PIP (Progeny) Age of Sampling Sample Tylosin group VTM FP MG group WK 27 WK 31 WK 35 WK 39 WK 43 WK 48 Wk 53 WK 64 DOC Neg Neg PIP Neg Neg DOC Neg Neg PIP Neg Neg DOC Neg Neg PIP Neg Neg DOC Neg Neg PIP Neg Neg DOC Neg Neg PIP Neg Neg DOC Neg Neg PIP Neg Neg DOC Neg Neg PIP Neg Neg DOC Neg Neg PIP Neg Neg Studies shows that possible Vertical transmission (transovarian/ Egg Transmission) are: 3 6 wk Post Infection : ~25-50% of eggs 8 15 wk Post Infection :~3 5% Based on serology, assuming the infection was in wk 48-49, hence, important to see that PCR result of DOC and PIP at wk 48, wk 53 and wk 64 in VTM FP-MG group is NEGATIVE.

37 Production Figure Summary Until 62 wks Standard VTM FP MG group Tylosin group DIFF (VTM Tylosin) Hen housed at 19 wks old 7,994 7,954 M+C Pullet (1 23 wks) 5.00% 6.53% 6.58 % % M+ C Laying stage (24 62 wks) 6.65% 8.40% 8.82% % Total Egg HH Hatching Eggs HH Sellable Chicks HH Total Sellable Chicks 1,005, , ,429

39 Ceva solutions Safer and Simpler vaccination Age Vaccination Application method Labor intensity Day old Vectormune ND + Cevac S.C injection XX MD Rispens ND + IB live Spray X I Day 10 ND + IB live Spray XX X Day 14 Gumboro Drinking water X X Day 26 Gumboro Drinking water X X Week 5 Vectormune FP-MG Wing web Week 8 Corymune 4k S.C injection XX XXX X X Week 14 Corymune 7K i.m. Injection XX XX 8 vaccinations in 18 wks 4 individual applications!!! Less applications = less stress, get full growth potential of young pullet!!

40 Simpler & Safer vaccination Vaccines Services Equipment From vaccine to vaccination & services

41 Thank you

Gumboro symposium 19 th & 20th of January 2012 BUDAPEST. Dr Sylvain COMTE Head of Poultry Franchise Poultry Corporate Marketing Director FRANCE

Ceva s Vision in poultry vaccination Gumboro symposium 19 th & 20th of January 2012 BUDAPEST Dr Sylvain COMTE Head of Poultry Franchise Poultry Corporate Marketing Director FRANCE Yann Arthus Bertrand