Marek s disease and vaccination Presented by Dr Peter Makang a

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1 Challenge poultry Marek s disease and vaccination Presented by Dr Peter Makang a

2 Economic impact of MD on the global poultry industry: 1 to 2 billion USD / year

3 Jozsef MAREK ( ) Multiple Nervenenzündung (Polyneuritis) bei Hühnern. Dtsch. Tierärztl. Wchschr.,

4 CLINICAL SIGNS

5 Stunting Depression Paleness in comb and wattles

6 Neurological signs

7 Blindness Picture: M. Putnam, 2010

8 Heart Lymphomas (Cardiovascular, respiratory & muscle) Normal Normal Affected Affected Normal Tumor Muscle Lungs

9 Liver Tumors Picture: M. Putnam, 2010

10 Neoplastic nerve lesions Sciatic Vagus & Brachial Vagus A N Sciatic A Loss of cross striations N

11 MECHANISMS

12 Inhalation of cell-free MDV in dander shed from FF 2-3 dpi Lung macrophages & DCs carry MDV to spleen, bf, thymus 5-6 dpi Cytolytic infection (necrosis) of B lymphocytes of spleen, bf, thymus I-suppr Immune response, recruitment of inflammatory cells: activated CD4 T cells, macrophages, heterophils, B cells 7-8 dpi MDV latency in CD4 T cells (spleen, PBL) Onset of protective CMI (CD8, NK) Dissemination from PBL: Transformation: 28 dpi 14 dpi 2 nd wave of cytolytic infection in epithelial tissues: I-suppr CD4 T-lymphomas in any tissue: nerves brain skin visceral organs Productive infection (fully infectious cell-free virions) in FFE SHEDDING TUMORS Gimeno I Vaccine 26S; C31-C41. Osterreider N. et al Nature Reviews 4;

13 VACCINES

14 MDV serotype New name Pathogenic Origin Vaccine strain Yes No Chicken Turkey Serotype 3 MeHV-1 X (naturally apathogenic) X (HVT) FC126, PB-THV1, HPRS-26

15 MDV serotype New name Pathogenic Origin Vaccine strain Yes No Chicken Turkey Serotype 3 MeHV-1 X (naturally apathogenic) Serotype 2 GaHV-3 X (naturally apathogenic) X X (HVT) FC126, PB-THV1, HPRS-26 SB1, 301B/1, HPRS-24

16 MDV serotype New name Pathogenic Origin Vaccine strain Yes No Chicken Turkey Serotype 3 MeHV-1 X (naturally apathogenic) Serotype 2 GaHV-3 X (naturally apathogenic) X Serotype 1 GaHV-2 X (HVT) FC126, PB-THV1, HPRS-26 SB1, 301B/1, HPRS-24 X X na X (attenuated derivatives) X CVI988 = Rispens, HPRS-16/att, R2/23, Clone C, C/R6

17 Two-step mechanism of protection: 1. Reduction of viraemia = less tumour formation + less immunosuppression; 2. Rejection of tumour cells by cytotoxic T cells. Baigent S.J. et al Vet Immunol Immunopathol 112; 78-86

18 COMBINING VACCINES FOR STRONGER PROTECTION?

19 Commercial birds: -shedders: ip inoculation of T.King strain (vv+mdv, not grown in cell culture) at 1 day of age; 2 weeks later, put in contact with vaccinates; -Vaccinates: sc vaccination at 1 day of age; put in contact with shedders either the next day of 5 days later. -Necropsy 8 weeks later. Vaccine Percent protection 1 dpv 5 dpv HVT + SB RISPENS RISPENS + HVT RISPENS + HVT + SB No clear benefit was provided by the triple combination. Rosenberger JK. 1995, Vineland Update 52.

20 Limitations of Marek vaccination: disease vaccination Baigent S.J. et al Vet Immunol Immunopathol 112; 78-86

21 DISEASE PATTERN HISTORY

22 Year Morbidity Mortality Age Clinical signs Vaccination approach 1907 (Marek J. et al.) Low Negligible Old Nerves inflammation «polyneuritis» - Gimeno I Vaccine 26S; C31-C41.

23 Year Morbidity Mortality Age Clinical signs Vaccination approach 1907 (Marek J. et al.) 1922 «mild» Low Negligible Old Higher Up to 20% Old Nerves inflammation «polyneuritis» Same as above + lymphoid tumors in visceral organs - - Gimeno I Vaccine 26S; C31-C41.

24 Year Morbidity Mortality Age Clinical signs Vaccination approach 1907 (Marek J. et al.) Low Negligible Old Nerves inflammation «polyneuritis» «mild» Higher Up to 20% Old Same as above + lymphoid tumors in visceral organs - End 1950s «vmdv» Higher Up to 30% Young Transient paralysis but mostly tumors - Evolution of MDV towards higher virulence: possible causes: Intensive methods of chicken production; Before vaccination started. Gimeno I Vaccine 26S; C31-C41.

25 Year Morbidity Mortality Age Clinical signs Vaccination approach 1907 (Marek J. et al.) 1922 «mild» End 1950s «vmdv» Low Negligible Old Higher Up to 20% Old Higher Up to 30% Young From 1969 onwards: Nerves inflammation «polyneuritis» Same as above + lymphoid tumors in visceral organs Transient paralysis but mostly tumors HVT Gimeno I Vaccine 26S; C31-C41.

26 Year Morbidity Mortality Age Clinical signs Vaccination approach 1907 (Marek J. et al.) 1922 «mild» End 1950s «vmdv» End 1970s «vvmdv» Low Negligible Old Higher Up to 20% Old Higher Up to 30% Young Higher From 1969 onwards: Nerves inflammation «polyneuritis» Same as above + lymphoid tumors in visceral organs Transient paralysis but mostly tumors MD breaks in vaccinated flocks USA: HVT+SB HVT ROW: Rispens Gimeno I Vaccine 26S; C31-C41.

27 Year Morbidity Mortality Age Clinical signs Vaccination approach 1907 (Marek J. et al.) 1922 «mild» End 1950s «vmdv» End 1970s «vvmdv» Mid-1990s «vv+mdv» Low Negligible Old Higher Up to 20% Old Higher Up to 30% Young Higher Higher From 1969 onwards: Nerves inflammation «polyneuritis» Same as above + lymphoid tumors in visceral organs Transient paralysis but mostly tumors MD breaks in vaccinated flocks MD breaks in vaccinated flocks, massive brain lesions, early mortality USA: HVT+SB1 USA: Rispens *: + revaccination, improving vacc tech, better control of other immsuppr diz HVT ROW: Rispens ROW: Rispens+HVT (+SB1) * Gimeno I Vaccine 26S; C31-C41.

28 CONCURRENT INFECTION WITH OTHER IMMUNOSUPPRESSIVE DISEASES IT CAN WORSEN THE OUTCOME

29 POSSIBLE CAUSES OF BREAKS

30 Induction of immunity, when vaccination is successful Stages of possible breaks Baigent S.J. et al Vet Immunol Immunopathol 112; 78-86

31 POSSIBLE USE FOR OTHER VACCINATION ND, IBD, AI

32 Vectorised Vaccines NDV D26 PEC promotor Donor Vector HVT FC 126

33 Duration of immunity

34 DOSE-EFFECT OF VACCINE ONE FULL DOSE / BIRD IS CRITICAL

35 Vaccine preparation Titre loss when ampoule is removed from LN2 tank, kept at room temperature and then replaced % - 97% 27 Controls 2,5 mn 5 mn Time of removal from the LN2 tank 3 Halvorson DA and DO Mitchell, 1979, Av Dis 24;

36 Vaccine preparation Titre loss when ampoule is thawed for a longer time than advised % - 22% - 53% seconds is an acceptable compromise Controls (30 sec) 5 mn 10 mn 15 mn Thawing time Halvorson DA and DO Mitchell, 1979, Av Dis 24;

37 Vaccine preparation Titre loss according to the temperature of the thawing bath % Controls (27 C) 17 C 40 C Temperature of the thawing bath 75-20% 80 Halvorson DA and DO Mitchell, 1979, Av Dis 24;

38 Vaccine preparation Titre loss according to the temperature of the diluent bag % 78 Controls (room temperature) Refrigerated (4 C) Temperature of the diluent bag Halvorson DA and DO Mitchell, 1979, Av Dis 24;

39 Préparation du vaccin Titre loss according to the rinsing procedure Controls (rinsed) - 14% 86 No rinse Halvorson DA and DO Mitchell, 1979, Av Dis 24;

40 Préparation du vaccin Titre loss according to the usage speed after reconstituion Controls (used within 2 hours) Used within 30 mn Halvorson DA and DO Mitchell, 1979, Av Dis 24;

41 Preparation and handling 41

42 Salle de vaccination

43 Vaccination 43

44 Vaccination 44

45 Conclusion We can significantly reduce Marek disease in the field if the following points are correctly combined 1. Vaccination correctly done (CHICK Program) : Dedicated team / trained and responsable Correct vaccine storage and preparation In a dedicated and clear environment The thawing procedure must be strictly respected Reliable and precise vaccination equipment 2. Farm control: Biosecurity Management Indicated vaccination program

Advances in Marek s Disease Vaccine Development:

Advances in Marek s Disease Vaccine Development: Michel Bublot, DVM, PhD - Merial R&D Asian Avian Forum 2016, Tokyo, July 12-13 Marek s Disease Control Good flock management Cleaning, disinfection Adequate