CEVA’S APPROACH F O R CONTROLLING GUMBORO DISEASE

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


VP2 Protein

Ag3 Ag4Ag1 Ag5 Ag6Ag7 Ag8

Ag9

Classical IBD virus : All Mabs bindings positive


VP2 Protein

Ag1 Ag5 Ag6Ag7 Ag8

Ag9

vv IBD virus : Bindings to Mab 3 and 4 are negative

- -


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


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

.


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)


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


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


Farm


Neighborhood

No IBD

Cevac Transmune IBDscl. IBD

vv IBD

CEVAC IBD L field use:

Is it immunosuppressive ?


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


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


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

)



Cevac IBD L use in a Turkish integration: impact on performances

241

316

0

50

100

150

200

250

300

EEC index



PI = livability x average slaughter BW / FCR

> 240: very good

210-240: good

180-210: medium

150-180: poor


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).


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.


Respective 2003 Turn Over of live IBD vaccines in 12 Western European countries

54%

46% Intermediate

Intermediate Plus


Respective 2004 Turn Over of live IBD vaccines in 12 Western European countries

55%

45%Intermediate

Intermediate Plus

CEVAC IBD L field use

BRAZIL


90,000 broiler chickens

Vaccination with CEVAC IBD L


5,57

3,01

0

1

2

3

4

5

6

Morta

lity (%

)

1

MORTALITY

Before CEVAC IBD L After CEVAC IBD L


2 1,92

0

0,5

1

1,5

2

2,5

FCR

1

FEED CONVERSION RATIO



52,7 54,1

0

10

20

30

40

50

60

Daily

wei

ght g

ain

(g/d

ay)

1

DAILY WEIGHT GAIN



242

272

0

50

100

150

200

250

300

Per

form

ance

inde

x

1

PERFORMANCE INDEX




Increased performances thanks to the optimum control of vvIBD in Brazil by Cevac IBD L.

COMMENTS

Other countries constantly report the same benefit.


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.


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 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.


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


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.


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


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.

..


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%


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.


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

????


The IMMUNE-COMPLEX concept (1988-1992)

It will CONTROL and PROTECT the vaccine virus:

Virus + Antiserum


The IMMUNE-COMPLEX concept (1988-1992)

MECHANISM ??


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 !!!


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


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


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


THANK YOU

FOR YOUR ATTENTION !

CEVA’S APPROACH F O R CONTROLLING GUMBORO DISEASE

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