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CEVA’S APPROACH FOR CONTROLLING GUMBORO DISEASE

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1 CEVA’S APPROACH FOR CONTROLLING GUMBORO DISEASE
CEVA SANTE ANIMALE CEVA’S APPROACH FOR CONTROLLING GUMBORO DISEASE By Dr. Vilmos PALYA Director of Viral Development, CEVA-PHYLAXIA BUDAPEST 19 October 2005

2 KANATLI BAĞIŞIKLIK SİSTEMİ
CEVA SANTE ANIMALE KANATLI BAĞIŞIKLIK SİSTEMİ

3 BAĞIŞIKLIK SİSTEMİNİN YAPISI VE İŞLEVİ
CEVA SANTE ANIMALE BAĞIŞIKLIK SİSTEMİNİN YAPISI VE İŞLEVİ Lymphoid organlar Primer: Thymus (T lymphocytes) Bursa fabricius (B lymphocytes) Sekonder: Dalak Harderian bezi Kemik iliği Konjuctival lymphoid doku (CALT) Bağırsak lymphoid dokusu (GALT) Başta lymfoid dokular (HALT) Bronşiyal lymphoid organlar (BALT)

4 Immune cells Lymphocytes: T cells B cells Mononuclear phagocytes
CEVA SANTE ANIMALE Immune cells Lymphocytes: T cells B cells Mononuclear phagocytes Tissue macrophages Follicular dendritic cells lymphocyte eosinophyl thrombocyte heterophyl monocyte

5 Bursal B hücre morfogenesisi

6 Bağışıklık hücrelerinin gelişimi
Civcivlerde inkübasyon periyodu: 21 days Bursa’da B hücrelerinin gelişimi: Follikule formasyonu (cortex, medulla) B hücrelerinde gen değişimi B hücrelerinin periferal bölgelere göçü Thymus’ta T hücrelerinin gelişimi Embryonasyonun 9.gününde T hücreleri gelişir T hücreleri çıkımdan sonra perifere göç eder Tavuk embriyoları spesifik immun cevabı başlatma yeteneğine sahiptirler In ovo aşılama

7 bağışıklık Natural or innate immunity Adaptive or acquired immunity
Cells Phagocytes, dendritic cells, NK cells T- and B-lymphocytes Humoral factors Complement system Cytokines Antibodies Interleukines Chemical property of identified structure Carbohydrate, lipid Protein Memory No Yes Protection Non-transferable Transferable Rapidity of the immune response Prompt Few days or week

8 Innate and adaptive immunity

9 Adaptive or acquired immunity
Active immunity specific immune response against antigens Primary response (first contact with antigen) IgM IgY Immune memory (B-ly) Secondary response (second contact with antigen) Rapid and longer immune response IgY Passive immunity Maternal antibody (transmitted from hen to chick via egg yolk) Transfusion of antibodies by sera

10 Passive immunity Maternally derived antibodies in offsprings
The level of the maternal antibodies can be increased by purposive immunisation of breeder flock Protect the chicks against diseases at early stage of life Antibodies decay 2-6 weeks after hatching The maternally derived antibodies neutralise the live vaccine viruses → inhibition of active immune response

11 Maternal immune transport in the chicken
FcRY transports IgY from yolk sac into embrionic blood (West et al., Immunity, 2004) pH dependent IgY binding to the yolk sac membrane the first IgY binding Fc receptor in birds

12 Humoral immune response I.
Three Ig classes: IgM, IgY, IgA IgM: pentamer, expressed on the surface of B cells IgY: functionally homologous to mammalian IgG IgA: dimeric or tetrameric forms in mucosal secretion monomeric molecule in serum critical role in local immunity Specific immune response Antigen → IgM class switching mediated by T cells and cytokines IgY or IgA Strong immune memory Methods for determination of antibody response: ELISA, SN, IF, agglutination, hemagglutination

13 Humoral immun cevap

14

15 Cell mediated immunity
T lympocytes are the principal cells in the cell mediated immunity Two subsets CD4+ cells: helper function – central role in humoral and cellular immunity CD8+ cells: cytotoxic function Important role in antiviral and antitumor immunity

16 Activity of different factors of immune system after viral infection

17 Chronic Bursitis after vvIBDV infection
Role of the bursa in immune response Gene conversion in B cells → humoral immunity Intact Bursa Fabricius Chronic Bursitis after vvIBDV infection

18 GUMBORO HASTALIĞI NEDİR
CEVA SANTE ANIMALE GUMBORO HASTALIĞI NEDİR

19 Infectious Bursal Disease Virus (IBDV)
Taxonomy: Family: Birnaviridae Genus: Avibirnavirus Virus properties: Virion not enveloped, 60nm diameter, icosahedral symmetry Two genome segments, Double stranded RNA genome Prof. Steward McNulty, Queen’s University of Belfast Segment B VP 1 VP2 VP4 VP3 VP5 Segment A

20 Infectious bursal disease (IBD, Gumboro disease)
Serotipeleri Serotype 1 and 2 Variant suşlar (serotip 1) Virulans bazlı grublanırsa Classical virulent IBDV Very virulent (vvIBDV) Moderately attenuated „intermedier plus”, „hot” Medium attenuated „intermedier” Heavily attenuated „mild” ] vaccine strains

21 Enfeksiyon ilk 3 hafta içerisinde immünosüpresyon nedenidir
3-6 haftalar içerisinde hastalığın klınik formu oluşur: Klınik bulgular enfeksiyondan 2-3 gün sonra Mortalite enfeksiyondan 5-8 gün sonra

22 IBDV infects cells of the cloacal bursa - primarily immature B-cells.
CEVA SANTE ANIMALE IBDV infects cells of the cloacal bursa - primarily immature B-cells. Immature B-cells mature into antibody producing cells. If B-cells are destroyed early in life the bird may become immunosuppressed for life.

23 CEVA SANTE ANIMALE Picture: Y. Gardin, 2003

24 Klınik görünümler

25 CEVA SANTE ANIMALE MORTALITE YAŞ(GÜN) Picture: Y. Gardin, 2003

26 Bursa histopatolojisi
CEVA SANTE ANIMALE Sağlıklı Bursa histopatolojisi Mersekelten karosodott, sulyosan karosodott, regeneralodo

27 CEVA SANTE ANIMALE Bursa büyüklüğü Gün From U. Lohren, 2005

28 IBD İMMÜNODEPRESSİF ETKİSİ
Immunodepresyon (ND antikor cevaplarına göre) Enfeksiyon yaşı (Gün) 1 ÖNEMLİ 7 ORTA DERECEDE 14 YOK 21 YOK (after Faragher et al, 1974)

29 Characterisation of the vvIBDV strains
Pathotyping Up to 100% mortality in SPF chickens 50-60% mortality in layers, 25-30% in broilers Break through higher levels of MDA  not possible anymore to protect passively broilers Antigenicity Panel of neutralizing Mabs  no (major) antigenic drift High cross-neutralization indices measured in SPF embryonnated eggs Classical serotype 1 vaccines still satisfactory on SPF birds Molecular characterisation Sequencing of the variable domain of the VP2 gene Amino acid residues substitutions at positions 222Ala, 256Iso, 294Iso and 299Ser = Genetic fingerprints of vvIBDV RT-PCR of vVP2 followed by sequencing and/or RE Analysis

30 Mortality rates Challenge of 5-week-old Lohmann SPF chickens (n=25-30) with 105 EID50 of IBDV strains of varying virulence in isolated conditions by the oculonasal route. vvIBDV induce higher mortality rates than classical virulent IBDVs Confusion in nomenclature Need for standardized challenge model

31 HİPERVIRULENT IBDV : MORTALİTENİN YAŞLA İLİŞKİSİ
120 Mortalite (%) 100 80 60 40 20 7 14 21 28 35 Bulaşma yaşı (gün) (after Meulemans et al, 1990)

32 Dose effect in IBDV challenge
Comparison of a classical virulent IBDV (Cu1wt) and a vvIBDV (HK46): Inoculation of increasing doses 103  107 EID50 Classical IBDV: maximum 60% mortality vvIBDV: up to 100% mortality Existence of a dose effect in IBDV challenge

33 Multiplication rates Titration of virus in BF of birds dying (or sacrificed) 3-4 days after challenge Higher multiplication rates for more virulent IBDVs 1 attenuated IBDV particle  10 particles 1 classical virulent IBDV particle  102 to 103 particles 1 vvIBDV particle  104 to 105 particles

34 PATOGENEZ VIRUS ETKİMESİ GÜÇLÜ VIRUS ZAYIF VIRUS YAŞ (GÜN) LEZYON +
MORTALITE GÜÇLÜ VIRUS LEZYON ZAYIF VIRUS ENFEKSİYON YOK 5 10 15 20 25 30 35 40 45 50 YAŞ (GÜN)

35 WHAT FORM OF GUMBORO DISEASE AT FIELD LEVEL ? WHICH CONTROL STRATEGY ?
CEVA SANTE ANIMALE WHAT FORM OF GUMBORO DISEASE AT FIELD LEVEL ? WHICH CONTROL STRATEGY ?

36 Laboratory tools From Di Fabio et al, 2000

37 OIE I. B. D. V. Classification N
OIE I.B.D.V. Classification N. Eterradossi - AFSSA Lab - Ploufragan France CAPSIDE ANTIGENS Characterisation by Monoclonal Antibodies (Mab) 8 Mab put in contact with the virus = bind or not. R.N.A. : Characterisation by sequencing: Sequence of Nucleotids and deduced a.a.

38 Specific Antigen-Capture ELISA
OIE I.B.D.V. Classification N. Eterradossi - AFSSA Lab - Ploufragan France Specific Antigen-Capture ELISA Revelation Mab specific Fixation or not Capture of the virus Polyclonal anti -IBDV

39 Classical IBD virus : All Mabs bindings positive
OIE I.B.D.V. Classification N. Eterradossi - AFSSA Lab - Ploufragan France Classical IBD virus : All Mabs bindings positive Ag1 Ag3 Ag4 Ag5 Ag6 Ag9 Ag7 Ag8 VP2 Protein

40 vv IBD virus : Bindings to Mab 3 and 4 are negative
OIE I.B.D.V. Classification N. Eterradossi - AFSSA Lab - Ploufragan France vv IBD virus : Bindings to Mab 3 and 4 are negative - - Ag1 Ag5 Ag6 Ag9 Ag7 Ag8 VP2 Protein

41 CEVA’S APPROACH OF GUMBORO CONTROL
CEVA SANTE ANIMALE CEVA’S APPROACH OF GUMBORO CONTROL

42 Results of the IBDV survey done by CEVA in 1999-2002 with AFSSA
Origin Mab 1 Mab 3 Mab4 Mab5 Mab6 Mab7 Mab8 Mab9 F52/70 (Classic) 66% 91% 78% 75% 110% 114% 96% 77% (vvIBD) 61% 1% 5% 68% 118% 113% 80% 53% Algeria 94% 4% 24% 90% 143% 153% 131% 49% Bulgaria 89% 3% 10% 77% 167% 172% 115% 78% Hungary 81% 1% 14% 72% 166% 174% 135% 74% India 65% 1% 10% 70% 121% 126% 81% 73% Iraq 74% 1% 10% 70% 121% 126% 81% 73% Jordan 106% 1% 11% 69% 206% 220% 167% 74% Kenya 104% 0% 11% 63% 192% 177% 144% 86% Malaysia 83% 123% 94% 61% 89% 106% 132% 38% Morocco 86% 1% 5% 83% 205% 189% 141% 62% Pakistan 94% 1% 7% 60% 181% 175% 137% 76% Romania 60% 2% 3% 37% 112% 105% 48% 78% Tanzania 79% 1% 20% 91% 131% 140% 118% 42% Tunisia 93% 0% 12% 73% 155% 162% 120% 91% Turkey 69% 1% 6% 54% 151% 152% 78% 102%

43 CEVAC IBD L Antigenic typing
CEVA’S APPROACH OF GUMBORO CONTROL CEVAC IBD L Antigenic typing Origin Mab 1 Mab 3 Mab4 Mab5 Mab6 Mab7 Mab8 Mab9 F52/70 (Classic) 66% 91% 78% 75% 110% 114% 96% 77% (vvIBD) 61% 1% 5% 68% 118% 113% 80% 53% Cevac IBD L 64% 89% 74% 23% 94% 93% 91% 91% CEVAC IBD L derived from classical IBDV strain and NOT from vvIBDV AFSSA 2001

44 Molecular typing of IBDV strains
PCR and sequencing Segment B VP 1 VP2 VP4 VP3 VP5 Segment A 709 Hypervariable region 1146 1. PCR reaction P1 P2 587 1229 2. PCR reaction P2.3 P5.3 721 1176 Nucleotide numbering according to IBDV-STC strain (Kibenge et al, J. Gen. Virol (71) ).

45 Differentiation of IBDV strains
CEVA’S APPROACH OF GUMBORO CONTROL Differentiation of IBDV strains (VP2 gene 414bp BseD I RFLP) CEVA OKYM 52/70 STC VarE LIBDV D69 50 bp DNA ladder 2512 Gp82 FS P3 IBD B.WSV IBD B.WSV D142 FS D69 AEG1 450 500 400 300 200 100 50 400 Jakabszállás 350 300 250 200 150 250 100 150 50 2512 vv vaccine classical var very virulent subc

46 Phylogenetic study of IBDV strains
CEVA’S APPROACH OF GUMBORO CONTROL MOH94/94H" MOH97/97H" Csengele/97H" PECS/97H" Phylogenetic study of IBDV strains OKYMT/95J DV86/86N vv OKYM/91J KABA/97H" UK661/86GB (based on the hypervariable region of the VP2 gene, 414bp) CS89/89GB FS/97H" AEG1/97H" Toszeg/97H" Diosjeno/97H" 849VB/87B vacc IBDL(2512)/80US" STC/67US classical P1II/75H" P1/75H" 52/70GB PBG98/76GB GP82/75H" D78" vacc TAD" Cu1/76D LIBDV/75H" P2/73D VarE/85US US var U28/88US VarA/85US 3212/88US serotype I GLS/87US P3/77H" P6/78H" subc P7/78H" P9/81H" P10/81H" serotype II P11/81H" 00273/73Aus OH/82US 19 18 16 14 12 10 8 6 4 2

47 CEVA’S APPROACH OF GUMBORO CONTROL
CEVA SANTE ANIMALE CEVA’S APPROACH OF GUMBORO CONTROL

48 Aşı türleri Canlı attenue Inaktive Mild Intermedier
Intermedier plus („hot”) İlk ve devamı aşılamalar için Inaktive Sadece canlı aşılama devamına Yüksek titre ve uzun süreli korunma

49 Conventional IBD Vaccines
Mild IBD Vaccine - Easily eliminated by low levels of maternal antibody. Intermediate Vaccine - relatively safe to use in ovo or at hatch. Eliminated by low to moderate levels of maternal immunity. Intermediate Plus Vaccine - not safe to give in ovo unless modified in some manner. Eliminated by high level maternal immunity.

50 IBDV aşılarının filogenetik grupları
D78 group IBDV aşılarının filogenetik grupları (Palya, 2003) P2 group 228E group 2512 group STC group MB group Lukert group V877 group

51 Aşı ve enfeksiyon sonu lezyon gelişimi (4 hft.SBF)
IDBV strains Days post infection 1 2 3 4 5 8 14 21 mild - intermedier ● R intermedier plus classical ●* very virulent vaccine strain [ * clinical signs, death ** 4-week old SPF birds R: regeneration

52 Immunity induced by strains of different virulence
** 4-week old SPF birds

53 Immunity induced by strains of different virulence - CONCLUSIONS -
Strains of higher virulence cause earlier bursa damage and earlier serological reponse Only strains that casue bursal damage induce immune response The tissue-culture adopted „mild” vaccine strain does not induced immune response in 4-week old SPF chicks (probably due to lack of receptors)

54 The influence of maternal antibody level on the replication of classical IBDV strain
positive bursa Infection at 11 days age negative bursa

55 Infection at 11 days of age
The influence of maternal antibody level on the replication of vv IBDV strain positive bursa Infection at 11 days of age negative bursa

56 Vaccination at 15 days of age
The influence of maternal antibody level on the replication of intermedier plus IBDV positive bursa Vaccination at 15 days of age negative bursa

57 Vaccination at 18 days of age
The influence of maternal antibody level on the replication of intermedier IBDV strain positive bursa Vaccination at 18 days of age negative bursa

58 IBD: The concept of constant protection
CEVA SANTE ANIMALE IBD: The concept of constant protection AGE AT VACCINATION VARIES ACCORDING TO VACCINE TYPE and EPIDEMIOLOGICAL SITUATION Antibody titre Passive immunity Vaccine take level Intermediate + V. Protection level v.v. IBDV Vaccine take level Intermediate V. Protection level Subclinical IBDV D1 Age Age at vaccination

59 Vaccination programme versus epidemiology
CEVA SANTE ANIMALE Vaccination programme versus epidemiology Farm No IBD scl. IBD vv IBD Neighborhood Mild Intermediate Intermediate plus

60 Farm No IBD scl. IBD vv IBD Cevac Bursa L Cevac Gumbo L Cevac IBD L
CEVA SANTE ANIMALE Farm No IBD scl. IBD vv IBD Neighborhood Cevac Bursa L Cevac Gumbo L Cevac IBD L

61 CEVA’S APPROACH OF GUMBORO CONTROL
CEVA SANTE ANIMALE CEVA’S APPROACH OF GUMBORO CONTROL Farm No IBD scl. IBD vv IBD Neighborhood Cevac Transmune IBD

62 CEVA’S APPROACH OF GUMBORO CONTROL Is it immunosuppressive ?
CEVAC IBD L field use: Is it immunosuppressive ?

63 CEVA’S APPROACH OF GUMBORO CONTROL
Economical Interest of Using an Intermediate Plus Vaccine in a Farm Contaminated with vvIBDV Intermediate plus vaccination Net income (FF/m2) 10 5 - 5 - 10 - 15 - 20 O Benefit level (After Y. Gardin, 1992) round 1 round 2 round 3 round 4

64 IMMUNOSUPPRESSION IN CHICKENS
CEVAC IBD L field use TURKEY

65 IMMUNOSUPPRESSION IN CHICKENS
CEVA SANTE ANIMALE IMMUNOSUPPRESSION IN CHICKENS

66 IMMUNOSUPPRESSION IN CHICKENS
CEVA SANTE ANIMALE IMMUNOSUPPRESSION IN CHICKENS

67 IMMUNOSUPPRESSION IN CHICKENS
CEVA SANTE ANIMALE IMMUNOSUPPRESSION IN CHICKENS PI = livability x average slaughter BW / FCR > 240: very good : good : medium : poor

68 IMMUNOSUPPRESSION IN CHICKENS
CEVA SANTE ANIMALE IMMUNOSUPPRESSION IN CHICKENS Intermediate Plus IBD live vaccines use in Europe: CEESA figures. CEESA means European Centre for Animal Health (Centre Europeen de la Sante Animale, in French).

69 IMMUNOSUPPRESSION IN CHICKENS
CEVA SANTE ANIMALE IMMUNOSUPPRESSION IN CHICKENS Intermediate Plus IBD live vaccines use in Europe: CEESA figures. It includes 12 countries: Austria, Belgium, Denmark, France, Germany, Italy, the Netherlands, Portugal, the Republic of Ireland, Spain, Switzerland, the United Kingdom.

70 IMMUNOSUPPRESSION IN CHICKENS
CEVA SANTE ANIMALE IMMUNOSUPPRESSION IN CHICKENS

71 IMMUNOSUPPRESSION IN CHICKENS
CEVA SANTE ANIMALE IMMUNOSUPPRESSION IN CHICKENS

72 IMMUNOSUPPRESSION IN CHICKENS
CEVAC IBD L field use BRAZIL

73 IMMUNOSUPPRESSION IN CHICKENS
90,000 broiler chickens Vaccination with CEVAC IBD L

74 IMMUNOSUPPRESSION IN CHICKENS

75 IMMUNOSUPPRESSION IN CHICKENS

76 IMMUNOSUPPRESSION IN CHICKENS

77 IMMUNOSUPPRESSION IN CHICKENS

78 IMMUNOSUPPRESSION IN CHICKENS
COMMENTS Increased performances thanks to the optimum control of vvIBD in Brazil by Cevac IBD L. Other countries constantly report the same benefit.

79 IMMUNOSUPPRESSION IN CHICKENS
COMMENTS Rate of usage of Cevac IBD L in the top 4 Brazilian broiler integrations in 2004 1 SADIA 100% 2 PERDIGAO 3 FRANGOSUL 0%* 4 SEARA * Use intermediate vaccine only.

80 IMMUNOSUPPRESSION IN CHICKENS
2005: Sadia (2nd largest Brazilian integration): Cevac IBD L is used in 100% of its capacity, i.e. 45 million broilers per month. From its introduction (2000) in Brazil, Cevac IBD L is now used at a rate of 140 million doses per month: Four Brazilian broiler chickens produced out of 10 are vaccinated using Cevac IBD L.

81 IMMUNOSUPPRESSION IN CHICKENS CEVAC IBD L Immunodepression study

82 IMMUNOSUPPRESSION IN CHICKENS
Immunosuppression study according to the European Pharmacopoeia requirements Ceva-Phylaxia study 11-day old SPF birds. Vaccination by eye drop (Day 0) with Cevac IBD L Control 50 birds per group. Four days later (D4, ie at maximum IBD vaccine replication in the bursa), ND vaccination by eye drop with Hitchner B1 strain (Cevac Uni L). ND challenge (Herts 33 strain, 106 EID50 per bird, by im route): day 18 (14 days after ND vaccination). ND challenge assessment: day 32.

83 IMMUNOSUPPRESSION IN CHICKENS

84 CONCLUSIONS Cevac IBD L is safe upon the immunological functions.
Cevac IBD L is the right tool to prevent vvIBD. Cevac IBD L is the right way to come back to performances and profits.

85 CEVA’S APPROACH OF GUMBORO CONTROL
CEVA SANTE ANIMALE CEVA’S APPROACH OF GUMBORO CONTROL And tomorrow… CEVAC TRANSMUNE IBD

86 Main issues around the protection against IBD:
CEVA SANTE ANIMALE IBD: INNOVATIVE VACCINATION STRATEGY Main issues around the protection against IBD: Differences in level of MDA Variability in quality of vaccine application Drinking water administration To adapt to the epidemiological context

87 Maternal antikor dağılımı
Homojen titreler C.V. = 29% Kötü dağılımlı titreler C.V. = 67% Heterojen titreler: C.V. = 114%

88 Cevac Transmune IBD CEVA’s answer to address these issues:
CEVA SANTE ANIMALE IBD: INNOVATIVE VACCINATION STRATEGY CEVA’s answer to address these issues: Cevac Transmune IBD Winterfield 2512 strain of IBDV Specific Antibodies Live, immune-complex vaccine Injected In-ovo, or Sub-cutaneous route at day-old

89 IBD: INNOVATIVE VACCINATION STRATEGY
Background Ability of the chick / the embryo to develop an immune response. 1985, Sharma: First in ovo Gumboro vaccination but MDA or safety problems: Mild vaccines: safe for Embryos but susceptible to MDA Intermediate and intermediate + vaccines: Efficacious in front of MDA but unsafe for SPF Embryos.

90 IBD: INNOVATIVE VACCINATION STRATEGY
SAFETY EFFICACY ????

91 Virus + Antiserum IBD: INNOVATIVE VACCINATION STRATEGY
The IMMUNE-COMPLEX concept ( ) It will CONTROL and PROTECT the vaccine virus: Virus + Antiserum

92 IBD: INNOVATIVE VACCINATION STRATEGY
The IMMUNE-COMPLEX concept ( ) MECHANISM ??

93 IBD: INNOVATIVE VACCINATION STRATEGY
1 / Antiserum neutralises the vaccine virus  embryo and vaccine are protected 2 / Progressively, the MDA are metabolised, as well as antiserum  Release of vaccine virus is synchronised with decrease of MDA 3 / When vaccine virus is stronger than antiserum + MDA action, it starts to replicate  and to Vaccinate !!!

94 IBD: INNOVATIVE VACCINATION STRATEGY
Antibody titre VACCINATION Age (days) Not protected chicken Protected chicken - 3 Maternally Derived Antibodies Protection on individual basis. Bird by bird !!! Active Immunity

95 CEVAC TRANSMUNE IBD 100% protection 100% protection 100% protection

96 Competitor vaccine dw 12 days
CEVAC TRANSMUNE IBD Protection of the Bursa of Fabricius after vvIBD challenge at 3,4,5 weeks of age (histology) Age at challenge 3 4 5 Cevac Transmune IBD SQ YES Competitor vaccine dw 12 days NO

97 CEVAC TRANSMUNE IBD

98 IBD: INNOVATIVE VACCINATION STRATEGY
Advantages of Cevac Transmune IBD Vaccination as soon as possible Mass vaccination – quick and correct Single vaccination – no follow-ups No need for date determination No effect of variable MDA levels Winterfield 2512 safety and efficacy Compatible with Marek vaccines, …

99 IBD: INNOVATIVE VACCINATION STRATEGY
THANK YOU FOR YOUR ATTENTION !


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