ceva’s approach for controlling gumboro disease by dr. vilmos palya director of viral development,...
TRANSCRIPT
CEVA’S APPROACH FOR CONTROLLING GUMBORO DISEASE
By
Dr. Vilmos PALYA
Director of Viral Development,
CEVA-PHYLAXIABUDAPEST
19 October 2005
KANATLI BAĞIŞIKLIK SİSTEMİ
BAĞIŞIKLIK SİSTEMİNİN YAPISI VE İŞLEVİ
Lymphoid organlarPrimer:
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)
Immune cellsLymphocytes:
T cells
B cells
Mononuclear phagocytes
Tissue macrophages
Follicular dendritic cells
lymphocyte
thrombocyte
eosinophyl
heterophyl
monocyte
Bursal B hücre morfogenesisi
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
Bağışıklık hücrelerinin gelişimi
Natural or innate immunity Adaptive or acquired immunity
Cells Phagocytes, dendritic cells, NK cells T- and B-lymphocytes
Humoral factorsComplement system
CytokinesAntibodies
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
bağışıklık
Innate and adaptive 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 immunityMaternal antibody (transmitted from hen to chick via egg yolk)
Transfusion of antibodies by sera
Adaptive or acquired immunity
Maternally derived antibodies in offspringsThe 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
Passive immunity
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
Maternal immune transport in the chicken
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 switchingmediated by T cells and cytokines
IgY or IgAStrong immune memory
Methods for determination of antibody response: ELISA, SN, IF, agglutination, hemagglutination
Humoral immune response I.
Humoral immun cevap
T lympocytes are the principal cells in the cell mediated immunity
Two subsetsCD4+ cells: helper function – central role in humoral and cellular
immunity
CD8+ cells: cytotoxic function
Important role in antiviral and antitumor immunity
Cell mediated immunity
Activity of different factors of immune system after viral infection
0 1 2 3 4 5 6 7 8 9 10 11 12 13days
rela
tive l
evel
IFN, IL NK cells Tc antibody virus titre
Role of the bursa in immune response
Gene conversion in B cells → humoral immunity
Intact Bursa Fabricius
Chronic Bursitis after vvIBDV infection
GUMBORO HASTALIĞI NEDİR
Infectious Bursal Disease Virus (IBDV)
Virus properties:
Virion not enveloped, 60nm diameter,
icosahedral symmetry
Two genome segments,
Double stranded RNA genome
Segment B
VP 1VP2 VP4 VP3VP5
Segment A
Taxonomy:
Family: Birnaviridae
Genus: Avibirnavirus
Prof. Steward McNulty, Queen’s University of Belfast
SerotipeleriSerotype 1 and 2Variant suşlar (serotip 1)
Virulans bazlı grublanırsaClassical virulent IBDVVery virulent (vvIBDV)Moderately attenuated
„intermedier plus”, „hot”Medium attenuated
„intermedier”Heavily attenuated
„mild”
Infectious bursal disease (IBD, Gumboro disease)
] vaccine strains
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
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.
Picture: Y. Gardin, 2003
Klınik görünümler
MORTALITE
YAŞ(GÜN)
Picture: Y. Gardin, 2003
Bursa histopatolojisi
Sağlıklı
Bursa büyüklüğü
Gün
From U. Lohren, 2005
IBD İMMÜNODEPRESSİF ETKİSİ
Enfeksiyon yaşı(Gün)
Immunodepresyon(ND antikor cevaplarına göre)
1 ÖNEMLİ
7 ORTA DERECEDE
14 YOK
21 YOK
(after Faragher et al, 1974)
Characterisation of the vvIBDV strainsCharacterisation 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
0
5
10
15
20
25
1 2 3 4
mortality
Mortality ratesMortality 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
0
20
40
60
80
100
849VB 96108 F52/70 Cu1wt VarE
IBDV strain
Mortality rates
HİPERVIRULENT IBDV : MORTALİTENİN YAŞLA İLİŞKİSİ
(after Meulemans et al, 1990)
0
20
40
60
80
100
120
0
Mortalite(%)
Bulaşma yaşı(gün)
7 14 21 28 35
Dose effect in IBDV challengeDose 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
Mortality rates
0102030405060708090
100
1 2 3 4 5 6 7
Titre (log10)
% m
ort
ali
ty
Classical IBDV
vvIBDV
Multiplication ratesMultiplication 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
Multiplication rate in BF
0
2
4
6
8
10
Attenuated Classical vvIBDV
IBDV strain
Tit
re (
log
10)
0 5 10 15 20 25 30 35 40 45 50
VIRUS ETKİMESİ
YAŞ (GÜN)
PATOGENEZ
LEZYON +
MORTALITE
LEZYON
ENFEKSİYON YOK
GÜÇLÜ VIRUS
ZAYIF VIRUS
WHAT FORM OF GUMBORO DISEASE AT FIELD LEVEL ?
WHICH CONTROL STRATEGY ?
Laboratory toolsLaboratory tools
From Di Fabio et al, 2000
OIE I.B.D.V. ClassificationN. Eterradossi - AFSSA Lab - Ploufragan France
R.N.A. :
Characterisation by sequencing: Sequence of Nucleotids and deduced a.a.
CAPSIDE ANTIGENS
Characterisation by Monoclonal Antibodies (Mab)
8 Mab put in contact with the virus = bind or not.
Specific Antigen-Capture ELISA
Mab
specific
Polyclonal anti -IBDV
Capture of the virus
Fixation or not
Revelation
OIE I.B.D.V. ClassificationN. Eterradossi - AFSSA Lab - Ploufragan France
VP2 Protein
Ag3 Ag4Ag1 Ag5 Ag6Ag7 Ag8
Ag9
Classical IBD virus : All Mabs bindings positive
OIE I.B.D.V. ClassificationN. Eterradossi - AFSSA Lab - Ploufragan France
VP2 Protein
Ag1 Ag5 Ag6Ag7 Ag8
Ag9
vv IBD virus : Bindings to Mab 3 and 4 are negative
- -
OIE I.B.D.V. ClassificationN. Eterradossi - AFSSA Lab - Ploufragan France
CEVA’S APPROACH OF GUMBORO CONTROL
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%89 163 (vvIBD) 61% 1%1% 5% 68% 118% 113% 80% 53%
Algeria 94% 4%4% 24%24% 90% 143% 153% 131% 49%Bulgaria 89% 3%3% 10%10% 77% 167% 172% 115% 78%Hungary 81% 1%1% 14%14% 72% 166% 174% 135% 74%India 65% 1%1% 10%10% 70% 121% 126% 81% 73%Iraq 74% 1%1% 10%10% 70% 121% 126% 81% 73%Jordan 106% 1%1% 11%11% 69% 206% 220% 167% 74%Kenya 104% 0%0% 11%11% 63% 192% 177% 144% 86%Malaysia 83% 123% 94% 61% 89% 106% 132% 38%Morocco 86% 1%1% 5%5% 83% 205% 189% 141% 62%Pakistan 94% 1%1% 7%7% 60% 181% 175% 137% 76%Romania 60% 2%2% 3%3% 37% 112% 105% 48% 78%Tanzania 79% 1%1% 20%20% 91% 131% 140% 118%42%Tunisia 93% 0%0% 12%12% 73% 155% 162% 120% 91%Turkey 69% 1%1% 6%6% 54% 151% 152% 78% 102%
Origin Mab 1 Mab 3 Mab4 Mab5 Mab6 Mab7 Mab8 Mab9
F52/70 (Classic) 66% 91%91% 78%78% 75% 110% 114% 96% 77%89 163 (vvIBD) 61% 1%1% 5% 68% 118% 113% 80% 53%
Cevac IBD L 64% 89% 74% 23% 94% 93% 91% 91%
CEVAC IBD L CEVAC IBD L derived fromderived from classical IBDV strain classical IBDV strain and and NOT NOT fromfrom vvIBDV vvIBDV
AFSSA 2001
CEVAC IBD L Antigenic typing
CEVA’S APPROACH OF GUMBORO CONTROL
Molecular typing of IBDV strains
Segment BVP 1VP2 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. 1990. (71) 569-577.).
PCR and sequencing
500400
300
200
100
50
Differentiation of IBDV strains Differentiation of IBDV strains (VP2 gene 414bp BseD I RFLP)
450
400
350
300
250
200
150
100
50
Gp
82
LIB
DV
2512
P3
OK
YM
52/7
0
ST
C
FS D69
IBD
B.W
SV
IBD
B.W
SV
D14
2
FS
D69
AE
G1
50 b
p D
NA
ladd
er
250
150
Var
E
vaccine classical var very virulent subc
CEVACEVA
vv2512
Jak
absz
állá
s 20
02.0
1.31
.
CEVA’S APPROACH OF GUMBORO CONTROL
19 024681012141618
MOH94/94H"MOH97/97H"
Csengele/97H"PECS/97H"
OKYMT/95JDV86/86N
OKYM/91JKABA/97H"
UK661/86GBCS89/89GBFS/97H"
AEG1/97H"Toszeg/97H"
Diosjeno/97H"849VB/87B
PBG98/76GBGP82/75H"
D78"TAD"
Cu1/76DLIBDV/75H"
P2/73DVarE/85US
U28/88USVarA/85US
3212/88USGLS/87US
52/70GBP1/75H"
P1II/75H"
STC/67USIBDL(2512)/80US"
P3/77H"P6/78H"P7/78H"
P9/81H"P10/81H"P11/81H"
00273/73AusOH/82US
Phylogenetic study of IBDV strainsPhylogenetic study of IBDV strains vv
classical
vacc
US var
subc
serotype I
serotype II
vacc
(based on the hypervariable region of the VP2 gene, 414bp)
CEVA’S APPROACH OF GUMBORO CONTROL
CEVA’S APPROACH OF GUMBORO CONTROL
Aşı türleri
Canlı attenueMildIntermedierIntermedier plus („hot”)
İlk ve devamı aşılamalar için
InaktiveSadece canlı aşılama devamınaYüksek titre ve uzun süreli korunma
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.
IBDV aşılarının filogenetik grupları
(Palya, 2003)
Distance 0.02
849VB/87BEDj/97HU
Nobilis Gumboro D78/INTERVETGumbovax Plus/ISBIBursa Blen/MERIAL
52/70GB
Miss
BG/RIAH
Tad Gumbovac Forte/LOHMANN
KABA/97HU
P3009
Delvax 228TC/Advance Pharma (INTERVET)
UK661/86GB
Soroa/ES
Tri-bio/IN
Bursine Plus/GeneBank
Univax/GeneBank
GLS/87US
Hipragumboro/HIPRA
FS/97HU
Poulvac/SOLVAY
Gumboro/OVEJERO
Izovac Gumboro3/IZO
D78/GeneBank
Izovac Gumboro2/IZOTAD Gumboro/TAD
Gumboral CT/MERIALCu1/76DE
BUR-706/MERIALGallivac IBD/MERIAL
GP82/CEVAPBG98/76GB
P2/73DELIBDV/CEVA
Hipragumboro CH/80/HIPRAGumbovax/IVAZ
228E/GeneBankNobilis Gumboro 228E/INTERVET
VarA/85USVarE/85US
2512/GeneBank2512/CEVA
Bursavac/GeneBankSTC/US
MB/ABICMB71/GeneBankIBD vaccine/VENTRIIV95/INDOVAX
PECS/97HUMOH94/94HU
OKYM/91JPOKYMT/95JP
Bursimune/BIOMUNEPoulvac Bursine2/FORT DODGE
V877/K/GeneBank00273/73Au
Bursavac live/GeneBankBursa Plus/FORT DODGE
MB group
STC group
2512 group
228E group
P2 group
D78 group
Lukert group
V877 group
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 ● R
intermedier plus
- ● ● ● ● ● ● R ● R
classical - ● ●* ●* ●* ● ● ●very virulent ● ● ●* ●* ●* ● ● ●
vaccine strain [* clinical signs, death** 4-week old SPF birdsR: regeneration
Immunity induced by strains of different virulence
0
2
4
6
8
10
12
14
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21Days post infection
log
2 E
LIS
A t
iter
mildintermedier plusintermediervery virulentclassical
** 4-week old SPF birds
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)
positive bursa
negative bursaInfection at 11 days age
2
4
6
8
10
12
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
log
2 V
N t
itre
on 4th days on 10th days
The influence of maternal antibody level on the replication of classical IBDV strain
Infection at 11 days of age
24
68
1012
0 2 4 6 8 10 12 14 16 18 20 22 24 26
log 2
VN
tit
re
on 4th day on 10th days
The influence of maternal antibody level on the replication of vv IBDV strain
positive bursa
negative bursa
2
4
6
8
10
12
0 2 4 6 8 10 12 14 16 18
log 2
VN
tit
re
on 4th days on 10th days daysdays napra
Vaccination at 15 days of agepositive bursa
negative bursa
The influence of maternal antibody level on the replication of intermedier plus IBDV
Vaccination at 18 days of age
2
4
6
8
10
12
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
log 2
VN
tit
re
on 4 th
days on 10th
days
The influence of maternal antibody level on the replication of intermedier IBDV strain
positive bursa
negative bursa
Antibody titre
D1 Age
Passive immunity
Age at vaccination
Protection levelSubclinical IBDV
Vaccine takelevel
Intermediate V.
AGE AT VACCINATION VARIES ACCORDING TO VACCINE TYPE and EPIDEMIOLOGICAL SITUATION
IBD: The concept of constant protection
Protection levelv.v. IBDV
Vaccine takelevel
Intermediate + V.
Farm
No IBD scl. IBD vv IBD
Neighborhood
No IBD Mild IntermediateIntermediate
plus
scl. IBD Intermediate IntermediateIntermediate
plus
vv IBDIntermediate
plusIntermediate
plusIntermediate
plus
Vaccination programme versus epidemiology
Farm
No IBD scl. IBD vv IBD
Neighborhood
No IBD Cevac Bursa L Cevac Gumbo L Cevac IBD L
scl. IBD Cevac Gumbo L Cevac Gumbo L Cevac IBD L
vv IBD Cevac IBD L Cevac IBD L Cevac IBD L
CEVA’S APPROACH OF GUMBORO CONTROL
Farm
No IBD scl. IBD vv IBD
Neighborhood
No IBD
Cevac Transmune IBDscl. IBD
vv IBD
CEVAC IBD L field use:
Is it immunosuppressive ?
CEVA’S APPROACH OF GUMBORO CONTROL
round 1 round 2
round 4
round 3
Intermediate plusvaccination
Net income (FF/m2)10
5
0
- 5
- 10
- 15
- 20
O Benefitlevel
(After Y. Gardin, 1992)
Economical Interest of Using an Intermediate Plus Vaccine in a Farm Contaminated with vvIBDV
CEVA’S APPROACH OF GUMBORO CONTROL
CEVAC IBD L field use
TURKEY
IMMUNOSUPPRESSION IN CHICKENS
Cevac IBD L use in a Turkish integration: impact on mortality20
8
0
4,5
0
2
4
6
8
10
12
14
16
18
20
IBD mortality Total mortality
Mor
talit
y ra
te (%
)
Before Cevac IBD L After Cevac IBD L
IMMUNOSUPPRESSION IN CHICKENS
Cevac IBD L use in a Turkish integration: impact on growth
2,2
2
2,5
1,8
0
1
2
3
BW at 42 d FCR
Bo
dy
wei
gh
t (kg
)
Before Cevac IBD L After Cevac IBD L
IMMUNOSUPPRESSION IN CHICKENS
Cevac IBD L use in a Turkish integration: impact on performances
241
316
0
50
100
150
200
250
300
EEC index
Before Cevac IBD L After Cevac IBD L
IMMUNOSUPPRESSION IN CHICKENS
PI = livability x average slaughter BW / FCR
> 240: very good
210-240: good
180-210: medium
150-180: poor
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).
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.
IMMUNOSUPPRESSION IN CHICKENS
Respective 2003 Turn Over of live IBD vaccines in 12 Western European countries
54%
46% Intermediate
Intermediate Plus
IMMUNOSUPPRESSION IN CHICKENS
Respective 2004 Turn Over of live IBD vaccines in 12 Western European countries
55%
45%Intermediate
Intermediate Plus
CEVAC IBD L field use
BRAZIL
IMMUNOSUPPRESSION IN CHICKENS
90,000 broiler chickens
Vaccination with CEVAC IBD L
IMMUNOSUPPRESSION IN CHICKENS
5,57
3,01
0
1
2
3
4
5
6
Morta
lity (%
)
1
MORTALITY
Before CEVAC IBD L After CEVAC IBD L
IMMUNOSUPPRESSION IN CHICKENS
2 1,92
0
0,5
1
1,5
2
2,5
FCR
1
FEED CONVERSION RATIO
Before CEVAC IBD L After CEVAC IBD L
IMMUNOSUPPRESSION IN CHICKENS
52,7 54,1
0
10
20
30
40
50
60
Daily
wei
ght g
ain
(g/d
ay)
1
DAILY WEIGHT GAIN
Before CEVAC IBD L After CEVAC IBD L
IMMUNOSUPPRESSION IN CHICKENS
242
272
0
50
100
150
200
250
300
Per
form
ance
inde
x
1
PERFORMANCE INDEX
Before CEVAC IBD L After CEVAC IBD L
IMMUNOSUPPRESSION IN CHICKENS
IMMUNOSUPPRESSION IN CHICKENS
Increased performances thanks to the optimum control of vvIBD in Brazil by Cevac IBD L.
COMMENTS
Other countries constantly report the same benefit.
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 100%
3 FRANGOSUL 0%*
4 SEARA 100%
* Use intermediate vaccine only.
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.
Four Brazilian broiler chickens produced out of 10
are vaccinated using
Cevac IBD L.
From its introduction (2000) in Brazil, Cevac IBD L is now used at a rate of 140 million doses per month:
CEVAC IBD L Immunodepression study
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.
IMMUNOSUPPRESSION IN CHICKENS
ND challenge in 11-day old SPF birds
100 100
00
10
20
30
40
50
60
70
80
90
100Pr
otec
tion
rate
(%)
Cevac IBD L + Uni L Cevac Uni L SPF controls
D0: IBD vaccinationD4: ND vaccinationD18: ND challengeD32: ND challenge assessment
IMMUNOSUPPRESSION IN CHICKENS
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.
CEVA’S APPROACH OF GUMBORO CONTROL
And tomorrow…
CEVAC TRANSMUNE IBD
IBD: INNOVATIVE VACCINATION STRATEGY
Main issues around the protection against IBD:
Differences in level of MDADifferences in level of MDA
Variability in quality of vaccine application Variability in quality of vaccine application
•Drinking water administrationDrinking water administration
To adapt to the epidemiological contextTo adapt to the epidemiological context
Maternal antikor dağılımı
0
1
2
3
4
5
6
7
8
0-14
9
150-
399
400-
999
1000
-199
9
2000
-299
9
3000
-399
9
4000
-499
9
5000
-599
9
6000
-799
9
8000
-999
9
1000
0-11
999
1200
0-14
999
1500
0-17
999
1800
0-21
999
2200
0-25
999
2600
0-29
999
3000
0-34
999
3500
0-40
999
ou p
lus.
..
ELISA titres classes
Num
ber
of birds
Mean = 2977 C.V.=29%
0
1
2
3
4
5
6
7
8
0-14
9
150-
399
400-
999
1000
-199
9
2000
-299
9
3000
-399
9
4000
-499
9
5000
-599
9
6000
-799
9
8000
-999
9
1000
0-11
999
1200
0-14
999
1500
0-17
999
1800
0-21
999
2200
0-25
999
2600
0-29
999
3000
0-34
999
3500
0-40
999
ELISA titres classes
Num
ber
of birds
Mean = 3923 C.V.= 67 %
012345678
0-14
9
150-
399
400-
999
1000
-199
9
2000
-299
9
3000
-399
9
4000
-499
9
5000
-599
9
6000
-799
9
8000
-999
9
1000
0-11
999
1200
0-14
999
1500
0-17
999
1800
0-21
999
2200
0-25
999
2600
0-29
999
3000
0-34
999
3500
0-40
999
ou p
lus.
..
ELISA titres classes
Num
ber
of b
irds
Mean = 7590 C.V. = 114%
Heterojen titreler: C.V. = 114%
Homojen titreler C.V. = 29%
Kötü dağılımlı titrelerC.V. = 67%
IBD: INNOVATIVE VACCINATION STRATEGY
CEVA’s answer to address these issues:CEVA’s answer to address these issues:
Cevac Transmune IBDCevac Transmune IBD
Winterfield 2512 strain of IBDVWinterfield 2512 strain of IBDV
Specific AntibodiesSpecific Antibodies
Live, immune-complex vaccineLive, immune-complex vaccine
InjectedInjected
•In-ovo, orIn-ovo, or
•Sub-cutaneous route at day-oldSub-cutaneous route at day-old
• Ability of the chick / the embryo to develop an immune response.
IBD: INNOVATIVE VACCINATION STRATEGY
Background
• 1985, Sharma: First in ovo Gumboro vaccination but MDA or safety problems:
• Intermediate and intermediate + vaccines: Efficacious in front of MDA but unsafe for SPF Embryos.
• Mild vaccines: safe for Embryos but susceptible to MDA
SAFETY EFFICACY
????
IBD: INNOVATIVE VACCINATION STRATEGY
The IMMUNE-COMPLEX concept (1988-1992)
It will CONTROL and PROTECT the vaccine virus:
Virus + Antiserum
IBD: INNOVATIVE VACCINATION STRATEGY
The IMMUNE-COMPLEX concept (1988-1992)
MECHANISM ??
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 !!!
IBD: INNOVATIVE VACCINATION STRATEGY
Antibody titre
VACCINATION
0 Age (days)
Not
protecte
d
chicken
Protecte
d
chicken
- 3
Maternally Derived Antibodies
Protection on individual basis.
Bird by bird !!!
Active Immunity
IBD: INNOVATIVE VACCINATION STRATEGY
CEVAC TRANSMUNE IBD
Cevac Transmune IBD in ovo: summary of serology kinetics in commercial broilers
0
2
4
6
8
10
12
14
0 7 14 21 28 35 42
Age (days)
IBD
VN
titr
e (l
og2)
Study 1 Study 2 Study 3 Study 4
100% protection
100% protection
100% protection
100% protection
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 SQYES YES YES
Competitor vaccine dw 12
daysNO NO YES
Cevac Transmune IBD SQ compared to the association of two intermediate vaccines: Protection rate after vvIBD challenge100
95
0
33
0
10
20
30
40
50
60
70
80
90
100
21 31Age at challenge (days)
Pro
tect
ion
(%)
Transmune Inter vacc (SQ 1d + dw 15d)
CEVAC TRANSMUNE IBD
IBD: INNOVATIVE VACCINATION STRATEGY
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, …
Advantages of Cevac Transmune IBD
IBD: INNOVATIVE VACCINATION STRATEGY
THANK YOU
FOR YOUR ATTENTION !