WPSA & WVPA Scientific Conference Roberto Soares, DVM, MAM, ACPV Regional Technical Manager - Poultry Ceva Animal Health APAC Malaysia

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1 WPSA & WVPA Scientific Conference 2013 Roberto Soares, DVM, MAM, ACPV Regional Technical Manager - Poultry Ceva Animal Health APAC Malaysia

2 Outlook the presentation Major changes in the Asia Poultry Industry Fast growth poultry industry Disease Challenge Role New technology vaccine for Newcastle Disease control Vector vaccines Evaluation Efficacy Compatibility Conclusions

3 Source: National geographic archive Population growth

4 By 2050 > 9 billion people will be living on Earth Source: National geographic archive

5 Nearly 60% in Asia 5

7 Main Source Protein 7

8 (million tones) E 140 (million tones)

Growth broiler meat production (1,000 MT) Country 2003 2012 Growth (%) China 9,898 13,700 + 38.4 India 1,500 3,160 + 110.7 Thailand 1,340 1,550 + 15.

9 Growth broiler meat production (1,000 MT) Country Growth (%) China 9,898 13, India 1,500 3, Thailand 1,340 1, Indonesia 1,118 1, Malaysia Philippines Vietnam Total 15,699 22, Source: USDA;

10 Changes in the Asia Poultry Industry Larger production units Strong disease pressure High stocking density Pressure to reduce the use anti-infectives Increased farm density Poorly qualified labour Marginally efficient respiratory system Reduced downtime period Complicated automation equipment Farms with different biosecurity standards closely located

11 Disease Challenge 12

12 Newcastle Disease Challenge 13

13 14

14 rhvt-nd

15 Recombinant ND vaccines Donor = NDV F protein NDV Genome NDV F protein F gene HVT F = Fusion Insertion site (nonessential sites on HVT genome) Vector = HVT virus rhvt - ND

16 How to evaluate a vaccine? Type immune response Onset Duration Level protection Ability evade MDA Reduce re-excretion Spectrum Compatibility 17

17 How to evaluate a vaccine? Type immune response Onset Duration Level protection Ability evade MDA Reduce re-excretion Spectrum Compatibility 18

18 Active Immune Response HI test is the most sensitive and specific method for the reliable detection the immune response induced by rhvt-ndv vaccine. Source: Palya et al. Monitoring the vaccination with a rhvt-ndv vectored vaccine in commercial broilers through serological methods. Poster at AAAP Meeting, San Diego CA, 2012.

19 Active Immune Response Cell-mediated. NDV specific cell mediated response 20

20 How to evaluate a vaccine? Type immune response Ability evade MDA Onset Reduce re-excretion Duration Spectrum Level protection Compatibility 21

% protection Onset Protection against vvndv challenge (Clinical protection) 100 80 60 40 20 0 W 2 W 3 W 4 W 6 rhvt-ndv Control Age challenge Broiler day-old chicks vaccinated with one full dose

21 % protection Onset Protection against vvndv challenge (Clinical protection) W 2 W 3 W 4 W 6 rhvt-ndv Control Age challenge Broiler day-old chicks vaccinated with one full dose rhvt-ndv vaccine. NDV challenges: Malaysian isolate ref. D1524/1/1,2/MY/10, viscerotropic velogenic NDV strain, genotype VII, 5 log 10 EID 50 /bird, nasal route (200 µl). Source: Extrated from Palya et al. Compatibility Vectormune ND with Cevac Transmune in day-old commercial broilers. SIS # 02/2012/P/SSIU CP, October 26, 2012.

% protection Onset Protection after ND challenge 100 80 60 Week 2 Week 3 Week 4 40 20 0 rhvt-ndv + live ND vaccine Control Layer day-old chicks vaccinated with one full dose rhvt-ndv & live ND

22 % protection Onset Protection after ND challenge Week 2 Week 3 Week rhvt-ndv + live ND vaccine Control Layer day-old chicks vaccinated with one full dose rhvt-ndv & live ND vaccines. NDV challenges done at 14, 21 and 28 days age with a velogenic ND virus (Thai Lopburi strain ICPI 1.86) at a dosage 10 5 EID 50 per bird by intramuscular injection. In high ND challenge areas, it is recommended to associate the rhvt-ndv with a live ND vaccine at day age. In some cases, a booster in the farms should be added. Source: Satra et al. Efficacy several vaccination programs against ND challenge. - WVPA Congress, Cancun, 2011.

23 rhvt-ndv vs rhvt-ndv Broiler day-old chicks were vaccinated subcutaneously with comparable doses the two rhvt-nd vaccines. A recent velogenic NDV isolate belonging to genotype VII (D1524/1/1,2/MY/10) was used for challenges. Clinical protection against NDV challenge was tested weekly from 3 to 6 weeks age. Source: Palya et al. Markedly different onset protection elicited by two HVT-based recombinat ND vaccines. Proceedings the WVPA Congress - Nantes, p. 448, August 2013.

% protection Results Clinical protection 100 Protection against vvndv challenge 80 60 40 20 0 W 3 W 4 W 5 W 6 rhvt-ndv 1 rhvt-ndv 2 Control Age challenge

24 % protection Results Clinical protection 100 Protection against vvndv challenge W 3 W 4 W 5 W 6 rhvt-ndv 1 rhvt-ndv 2 Control Age challenge Source: Palya et al. Markedly different onset protection elicited by two HVT-based recombinat ND vaccines. Proceedings the WVPA Congress - Nantes, p. 448, August 2013.

25 How to evaluate a vaccine? Type immune response Onset Duration Level protection Ability evade MDA Reduce re-excretion Spectrum Compatibility 26

26 Material & Methods Commercial laying pullets. Challenge with a Genotype VII strain (Malaysian isolate) 5.0 log 10 EID 50 /bird by intranasal route (0.1 ml) Group Weeks age rhvt-ndv * Group 2 rhvt-ndv + Live ND vacc ND Killed Groups 3 rhvt-ndv + Live ND vacc LaSota ND Killed Groups 4 Negative & Positive Control groups - No vaccination Monitoring parameters (during 14 days): Daily observations for NDV specific clinical signs, mortality and egg production (33 wk challenge) * Effect NDV challenge on the egg production

Clinical protection NB: VTM-ND & Vitapest & LaSota & killed group was challenged only 4 weeks after LaSota booster (before vaccination with the killed ND

27 Clinical protection NB: VTM-ND & Vitapest & LaSota & killed group was challenged only 4 weeks after LaSota booster (before vaccination with the killed ND vaccine) and at 55 wks age. Under the conditions this trial, the rhvt-ndv vaccine alone induced a strong (clinical signs + shedding controls) up to 72 weeks age.

28 How to evaluate a vaccine? Type immune response Onset Duration Level protection Ability evade MDA Reduce re-excretion Spectrum Compatibility 29

29 Materials & Methods Commercial broilers (20 per group) rhvt-ndv SQ or in-ovo (-3d) Challenge : 10 5 EID 50 Chimalhuacan NDV strain (Genotype V) at 3 or 4 or 6 weeks age IN + ON route Oropharyngeal and Cloacal swabs taken 3 and 7 days post challenge Virus quantification using RT-PCR

30 Clinical protection Results

31 Results Reduction shedding Challenge at D27 * * * * * * * *

32 Results Reduction shedding Challenge at D40 * * * * * * * *

33 How to evaluate a vaccine? Type immune response Onset Duration Level protection Ability evade MDA Reduce re-excretion Spectrum Compatibility 35

34 Spectrum Does it protect against various types NDV? Yes! Yes! Yes! F insert Yes!

35 How to evaluate a vaccine? Type immune response Onset Duration Level protection Ability evade MDA Reduce re-excretion Spectrum Compatibility 37

36 Compatibility rhvt-nd Rispens

37 39

38 Compatibility studies rhvt-nd HVT

Conclusions The poultry industry has developed remarkably in the recent years. Genetic improvement, nutrition, husbandry, housing systems, animal health etc.

40 Conclusions The poultry industry has developed remarkably in the recent years. Genetic improvement, nutrition, husbandry, housing systems, animal health etc. New technology vaccine plays an important role in the control Newcastle Disease Safe Prevent clinical signs Reduces shedding Induces strong and persistent 42

RECOMBINANT VACCINES Live or Killed

Antigens and Vaccines Molecular biology drives Innovation Antigen Gene of Interest Recombination RECOMBINANT VACCINES Live or Killed Antigens and Vaccines Molecular biology drives Innovation Antigen Gene