Number 1

MER IAL TECHNICAL NEWSLET TER

eld infection

4. Improved performance with VAXXITEK HVT+IBD vaccination

1. Atienza JC, Nagera AJ, Martinez PO, Baysac ND, Castillo MT, Damaso VR, Lemière S. Evaluation of a herpesvirus of turkey vector vaccine inducing protection against infectious bursal and Marek’s diseases (VAXXITEK® HVT+IBD) under Philippines

Poultry Congress, Brisbane, Australia. 2008. Article wpc0801684, 9 p.

Use of a vectored vaccine against infectious bursal disease of chickens in the face of high-titred maternally derived antibody. Journal of Comparative Pathology, 2007;137:81-84.

3. Darteil R, Bublot M, Laplace E, Bouquet JF,

recombinant viruses expressing infectious bursal disease virus (IBDV) VP2 immunogen induce

protection against an IBDV virulent challenge in chickens. Virology, 1995;211:481-490.

Menendez A, Ruiz H et al cacy in broiler chickens in Latin America of vHVT-013, a Marek’s HVT vector vaccine expressing VP2 in infectious bursal disease virus. Oral presentation and abstract at the 15th congress of the World Veterinary Poultry Association, 2007; p199.

cacy of a recombinant vaccine HVT-VP2 against Gumboro disease in the presence of maternal antibodies. British Poultry Science, 2003;44:824-825.

6. Le Gros F-X, Dancer A, Giacomini C, Pizzoni L, cacy trial of

a novel HVT-IBD vector vaccine for 1-day-old broilers. Vaccine, 2009;27:592-596.

7. Lemière S. Marek’s virus vector vaccines inducing protection against Marek’s disease and infectious

abstract at the 8th International Marek’s Disease Symposium, Townsville, Australia. 2008. p75.

8. Massi P, Tosi G, Fiorentini L. Experimental challenge trial with a «very virulent» strain of Infectious Bursal Disease virus (vvIBDV) in commercial pullets vaccinated with an IBD vectored vaccine or with

International, November 2008;50-57.

9. Prandini F, Bublot M, Le Gros F-X, Dancer A, Pizzoni L, Lamichhane C. Assessment of the immune response in broilers and pullets using two ELISA lits after in ovo or day-old vaccination with a vectored HVT+IBD vaccine (VAXXITEK HVT+IBD). Zootecnica International, September 2008;40-50.

References

- 4 -

ocks is critical for as- cacy and antibody per-

eld infections that could have dramatic consequences. However, classical IBD ELISA tests do not easily allow for

erentiation between infected chickens and chickens vaccinated with MLVs. This is a prob-lem, particularly when bursal lesions are ob-served. A way to distinguish vaccinated from infected birds is to perform RT-PCR on IBDv strains responsible for the bursal lesions.

With the use of the VAXXITEK HVT+IBD vac- erentiate susceptible,

immunised and infected chickens on the basis of the anti-IBDv antibody response obtained by a test that uses two ELISA kits: the ProFLOK® IBD Ab test kit and the ProFLOK® IBD Plus Ab test kit. The IBD Ab test kit detects antibod-ies mainly against the VP3 antigen, present in

ed live vaccine viruses, but not in the VAXXITEK HVT+IBD vac-cine; the IBD Plus Ab test kit detects more spe-

cally antibodies raised against the VP2 an- eld and

vaccine viruses. This test kit is very sensitive and highly correlates with the virus neutraliza-

ects the protection against IBDv.

eld to monitor the appearance of protective antibodies after vaccination, with no risk of interference with infection-induced antibodies, and to show the absence of an immunity gap (6).

This approach has been successfully used in ocks in several

countries (France, Italy, Hungary) and allowed erentiation of chickens vaccinated

with VAXXITEK HVT+IBD from IBD-infected chickens, while chickens vaccinated with MLVs could not be distinguished from infected chickens (9).

®VAXXITEK is a registered trademark of Merial in the United States of America and elsewhere.

MERIAL - 29, avenue Tony Garnier, 69007 LYON - FRANCETél.: 33 (0)4 72 72 30 00Fax: 33 (0) 72 72 30 69

- 1 -

Figure 2 – Mortality monitoring - Philippines trials

25

20

15

10

5

0

% m

orta

bilit

y

82D laniF12D41D7D

Farm1VAXXITEK HVT+IBDFarm2VAXXITEK HVT+IBDFarm3VAXXITEK HVT+IBDFarm1ControlFarm2 ControlFarm3 Control

Figure 3 – Feed conversion index monitoring - Philippines trials

2,50

2,00

1,50

1,00

0,50

0,00D7 D14 D21 FinalD28

Feed

Con

vers

ion

Inde

x

Farm1VAXXITEK HVT+IBD

Farm2VAXXITEK HVT+IBD

Farm3VAXXITEK HVT+IBD

Farm1Control

Farm2 Control

Farm3 Control

®ProFLOCK is a registered trademark of Synbiotics, Corporation in the United States of America and elsewhere.

Table 4 – Return on investment following vaccination with VAXXITEK HVT+IBD (adapted from Atienza et al, 2008)

Farm 1 Control VAXXITEK Control VAXXITEK ControlVAXXITEK

HVT+IBD HVT+IBD HVT+IBD Average daily gain (g) 48.49 48.25 37.52 35.57 50.33 47.81 European Performance index 287.25 261.44 156.72 124.30 240.27 190.11 Feed cost per bird (US $) $1.19 $1.31 $1.23 $1.28 $1.50 $1.69 Computed cost advantage per bird (US $) $0.13 $0.19 $0.27

4.1. Mortality and bursal protection eld performance of VAXXITEK HVT+IBD

eld trials eld trial in the Philippines

found only low grade bursal lesions post-vacci- rming that the VAXXITEK HVT+IBD

vaccine is safer than conventional vaccines in ocks vac-

cinated with VAXXITEK HVT+IBD were better protected against naturally occurring infection

ocks vaccinated with classical IBD vaccines: no clinical IBD was ob-served in these historically positive farms after vaccination with VAXXITEK HVT+IBD (1).

eld trials conducted in the Philippines and in Latin America, where classical, vvIBD and variant strains have been reported, mortality in broiler chickens vaccinated with VAXXITEK HVT+IBD was found to be much lower than in control birds vaccinated with MLVs (1,4). In the Philippines trial, bursa size, bursa weight and bursa-to-body weight ratio were found to be higher, and bursal lesion scores lower,

ocks vaccinated with VAXXITEK HVT+IBD ocks vaccinated with classical IBD

ocks vaccinated with conventional IBD vaccines (1) (Figure 2).

4.2. Growth performanceVAXXITEK HVT+IBD contributes to the devel-opment of a strong immune system and a de-creased risk of respiratory problems noticed

eld trials. Immune integrity results in ock,

as energy from feed is utilized for growth rather diseases. In broiler production,

an improvement in production performance t.

Growth parameters of VAXXITEK HVT+IBD birds eld have consistently been

found to be better than those of control groups with higher mean body weight, lower feed conversion ratio and lower mor-tality (4). In the Philippines trial, both lifetime average live weight and feed conversion ratio were

ocks vaccinated

4.3. Return on investment eld trials conducted in Latin

America (Venezuela, Peru and Brazil), the use of VAXXITEK HVT+IBD resulted in increased productivity and economic ben-

ts (Fernandez et al, 2007). The Philippines trial showed that, in practice, the use of VAXXITEK HVT+IBD in farms translates into a higher average daily gain, a higher European Performance Index (EPI) and lower feed cost per bird, compared to the use of classical IBD vaccines. This data provides evidence that the use of VAXXITEK HVT+IBD is cost-

ective, as shown by a com-puted cost advantage per bird observed in all study farms. (1) (Table 4).

Editorial

ective against classic, very virulent and variant IBD viruses, and can be used in most rst launched in 2006 in Brazil; it is now used across the globe,

rst published the preliminary work on the HVT IBD vector vaccine in 1995. Interest in the vaccine increased c journals and presentations at international avian congresses around 2003.

ts of using VAXXITEK HVT+IBD have come out. Studies have also been published on diagnostic tools for distinguishing birds vaccinated with VAXXITEK HVT+IBD from infected birds, which can be used to monitor the immune response to vaccination.

We hope that you enjoy reading VAXXITEK NEWS and invite you to discover and read our published papers

Stéphane LEMIÈREAvian Global Technical Director

Number 1

Farm 3Farm 2

Number 1Number 1

VAXXITEK® HVT+IBD, Merial’s innovative IBD vaccine: a safe ine for broad, sustained protection of chickens

ectively against cantly impact the poultry industry, Marek’s disease (MD) and

including classical, variant and very virulent strains. It can be administered in ovo or to 1-day-old chicks by sub-cutaneous

and MD even in the presence of high levels of maternal antibodies, and eliminates the immunity gap observed with

diseases to broiler and layer chickens. By protecting immune system integrity, it protects from a variety of infectious

return on investment. Vaccinated and protected chickens can be distinguished serologically from infected birds.

cacy demonstrated in experimental studies

are at their highest, VAXXITEK HVT+IBD in- cient and early immune response

both in broilers and pullets under experimen- eld. Studies

show that no immunity gap occurs during the

eld challenge. On the contrary, an immunity gap has been observed in birds vac-cinated with a registered MLV administered at

Full protection against bursal lesions induced by challenge with classical IBD or IBD vari-ant viruses has been observed as soon as

protection against experimental 3.2. Period of susceptibility-lasting

IBDv exposureThe immune response induced by VAXXITEK HVT+IBD provides early protection against IBDv that lasts during the whole period of susceptibili-ty to the IBDv. Protection refers to the prevention of mortality and the reduction of clinical signs, as well as lesions due the IBD viruses depending upon the context of the clinical studies.

The immunity conferred by VAXXITEK HVT+IBD is long-lasting, without need for booster vacci-

et al. observed high antibody

pullets vaccinated with VAXXITEK HVT+IBD at

In a study by Goutebroze et al., broilers vacci-

were fully protected against vvIBDv challenge

Massi et al. found that pullets were also fully

of age; no clinical signs, no gross lesions and

lets vaccinated with VAXXITEK HVT+IBD, while

groups of chickens vaccinated with commer- ecting IBD-

induced immunodepression, like bursa weight and bursa-to-body weight ratios, were only

group, while they were dramatically decreased

eld con-ditions, VAXXITEK HVT+IBD vaccinated broil-ers were better protected against IBDv after challenge with the vvIBDv 91-1928 strain or

eld vi-ruses) compared to chickens vaccinated with other commercial vaccines, in terms of devel-opment of IBD clinical symptoms and mortal-

cient protection against

VAXXITEK HVT+IBD protects chickens against eld strains, including

vvIBD and classical IBD, and against IBD vari-ant viruses. Laboratory tests showed that 95 to 100% of chickens vaccinated either in ovo or

lenge with various IBDv strains: the USDA (STC)

1. Introduction

Marek’s Disease (MD) and Infectious Bursal Disease (IBD), also called Gumboro disease, are the two most common immunosuppres-

ect the poultry in-dustry. MD is a common lymphoproliferative disease caused by a herpesvirus (Marek’s Dis-ease virus or MDv). Control of Marek’s disease has been achieved in the poultry industry since the 1970’s with the large-scale use of turkey herpesvirus (HVT) vaccines. Infectious bursal disease is a highly contagious infection of chickens caused by a birnavirus (IBDv) that destroys lymphocytes in the bursa of Fabricius

rst recognised more cant

economic losses in the poultry industry world-wide. In the late 1980’s a very virulent strain of

ocks in Europe and rapidly spread across the globe.

old, depending on their level of maternal im-munity against the disease. The clinical form of IBD usually occurs in chickens from 3 to

increase of mortality rate. The most frequent and economically important form of the dis-ease is subclinical and occurs in chickens less

signs of disease, but experience permanent and severe immunosuppression, reduced an-tibody response to vaccination and increased susceptibility to concurrent or secondary in-fections.

2.1. IBD vaccination,

A new vaccine, VAXXITEK HVT + IBD, combines the advantages of a live vaccine against IBDv without its safety problems and allows for ear-ly vaccination against both MD and IBD viruses (including classic, variant and very virulent IBD strains).

Early protection of chicks is key in prevent-ing IBD; this can be achieved through passive protection which is obtained by vaccinating breeding hens with inactivated IBDv vaccines. Maternal antibodies (MDAs) are transmitted to the progeny through the egg yolk to provide

life, and then titres decline. Protection against IBDv must then be maintained by administer-

ed live vaccines (MLVs).

However, MDA levels are highly variable cacy

and safety of MLVs remains an unsolved is-

the time of vaccination neutralize the vac-cine virus, chicks are generally vaccinated at

sub-protective levels. Then, approximately

to develop minimal protective titres, leaving an immunity gap between approximately 15

susceptible to IBD.

Various MLVs have been developed and clas- ed as “mild”, “intermediate” and “hot” IBD

c ca-

cy in the presence of anti-IBDv MDAs is poor. Protection provided by “intermediate” and “hot” vaccines is much higher, but these vac-cines retain some pathogenicity: they induce bursal lesions (2).

Co-administration of live MD and IBD vaccines as early as possible (ie. in day-old chicks or in ovo) has been proposed in order to induce early protection against both immunosup-pressive diseases, however this approach has

cacy prob-

2.2. VAXXITEK HVT+IBD:

VAXXITEK HVT+IBD is a live vector vaccine in which turkey herpesvirus (HVT), the most widely used MD vaccine on the market, is used as a vector expressing an IBDv antigen (VP2) (3). The HVT vaccine is well-known to be safe and poorly sensitive to interference from MDAs. VP2 is one of the major structural pro-teins of the virus, and the major host-protec-tive antigen to IBDv, containing at least three independent epitopes responsible for the in-duction of neutralizing antibodies.The vector vaccine strain is obtained by inser-tion of the IBDv VP2 gene from the Faragher 52/70 strain into the HVT virus. Its expression during vector replication triggers an immune response that protects against all types of IBDv strains (classic, variant and very viru-lent strains) (8). Since no IBDv gene respon-sible for bursal lesions is present in the vector, VAXXITEK HVT+IBD is safe, and can be admin-istered by subcutaneous injection in 1-day-old SPF chicks or by the in ovo route during trans-fer from setters to hatchers in the hatchery,

No visible gross pathological changes or sig- cant microscopic lesions of the bursa have

of 1-day-old chicks (2).

®VAXXITEK is a registered trademark of Merial in the United States of America and elsewhere.- 2 - - 3 -

cacy and safety.

isolate, the homologous Faragher 52/70 strain, the French vvIBDv strain (91168), a vvIBDv

eld isolate and a US variant E strain. Protection was evaluated either by observ-

(STC), by scoring microscopical lesions of the bursa (52/70 and 91-168), by measuring the bursa lesion score (Italian isolate) or by mea-

3.4.

3.1. Preventing the immunity gap

protectionSince VAXXITEK HVT+IBD only triggers the expression of the IBDv VP2 gene, it does not

express any gene responsible for IBDv patho-genicity: it does not induce bursal lesions in contrast to conventional MLV vaccines, even those with intermediate strains.Several experimental studies have shown that

the integrity of the bursa of Fabricius, the main target of IBDv. After challenge with various IBDv strains, bursal characteristics of vaccinat-ed broilers and pullets (size, weight, presence of microscopic or gross lesions) have been shown to be unchanged or better than those of unvaccinated birds or birds vaccinated with

Table 2a – Protection provided by vaccination of broilers with VAXXITEK HVT + IBD against experimental challenge (adapted from Goutebroze et al, 2003).

Experimental conditions

Protection against challenge with the vvIBDV 91-168 strain Broilers Challenge at 3 weeks of age

20 broilers 20 broilersChallenge at 6 weeks of age

VAXXITEK HVT + IBD (at 1 day of age)

VAXXITEK HVT + IBD yes 0/15 0/15 “Intermediate” vaccine A yes 2/15 2/15 “Intermediate” vaccine B yes 2/15 2/15 “Intermediate plus” vaccine C yes 2/15 1/15 Unvaccinated, challenged yes 15/15 2/15 Unvaccinated, unchallenged no 0/15 0/15

Full protection Full protection Antibody titre (maternal) = 1:8910 Antibody titre = 1:1 890 Controls

Antibody titre = 1:18

Experimental Persisting plateau of high levels of conditions seroneutralizing anti-IBDv antibodies reached Bublot et al, 2007 Broilers at about 6 weeks of age Field Active immune response at 3-4 weeks of age / conditions immunity gap in control birds vaccinated with a Le Gros et al, 2009 registered attenuated intermediate IBD vaccine Broilers & Field Active and strong anti-VP2 response observed Prandini et al, 2008 pullets conditions from 15 days of age

assi et al, 2008).

Pullets Italian strain at 6 weeks of age of IBD

Table 3 – Broad protection and preserved bursa integrity upon vaccination with VAXXITEK HVT+IBD.

Challenge strain Parameter evaluated Results Reference Broilers Size of bursa of Fabricius et al, than than unvaccinated controls 2003 SPF Presence of No microscopical lesions (lesions Bublot et al, 2007 microscopical lesions in 70% of controls) SPF STC strain Bublot et al, 2007 bursal lesions challenge, no matter the time of challenge Bursa-to-body weight Higher bursa-to-body weight ratio SPF variant E strain ratio 10 days after challenge when compared Bublot et al, 2007 to unvaccinated challenged controls Pullets isolate score 11 days after challenge, compared to birds Massi et al, 2008 vaccinated with MLV strains

vvIBD 91168 strain

®VAXXITEK is a registered trademark of Merial in the United States of America and elsewhere.

Bursal

Trial Immunity Reference

30

30%30%

Number 1Number 1

VAXXITEK® HVT+IBD, Merial’s innovative IBD vaccine: a safe ine for broad, sustained protection of chickens

ectively against cantly impact the poultry industry, Marek’s disease (MD) and

including classical, variant and very virulent strains. It can be administered in ovo or to 1-day-old chicks by sub-cutaneous

and MD even in the presence of high levels of maternal antibodies, and eliminates the immunity gap observed with

diseases to broiler and layer chickens. By protecting immune system integrity, it protects from a variety of infectious

return on investment. Vaccinated and protected chickens can be distinguished serologically from infected birds.

cacy demonstrated in experimental studies

are at their highest, VAXXITEK HVT+IBD in- cient and early immune response

both in broilers and pullets under experimen- eld. Studies

show that no immunity gap occurs during the

eld challenge. On the contrary, an immunity gap has been observed in birds vac-cinated with a registered MLV administered at

Full protection against bursal lesions induced by challenge with classical IBD or IBD vari-ant viruses has been observed as soon as

protection against experimental 3.2. Period of susceptibility-lasting

IBDv exposureThe immune response induced by VAXXITEK HVT+IBD provides early protection against IBDv that lasts during the whole period of susceptibili-ty to the IBDv. Protection refers to the prevention of mortality and the reduction of clinical signs, as well as lesions due the IBD viruses depending upon the context of the clinical studies.

The immunity conferred by VAXXITEK HVT+IBD is long-lasting, without need for booster vacci-

et al. observed high antibody

pullets vaccinated with VAXXITEK HVT+IBD at

In a study by Goutebroze et al., broilers vacci-

were fully protected against vvIBDv challenge

Massi et al. found that pullets were also fully

of age; no clinical signs, no gross lesions and

lets vaccinated with VAXXITEK HVT+IBD, while

groups of chickens vaccinated with commer- ecting IBD-

induced immunodepression, like bursa weight and bursa-to-body weight ratios, were only

group, while they were dramatically decreased

eld con-ditions, VAXXITEK HVT+IBD vaccinated broil-ers were better protected against IBDv after challenge with the vvIBDv 91-1928 strain or

eld vi-ruses) compared to chickens vaccinated with other commercial vaccines, in terms of devel-opment of IBD clinical symptoms and mortal-

cient protection against

VAXXITEK HVT+IBD protects chickens against eld strains, including

vvIBD and classical IBD, and against IBD vari-ant viruses. Laboratory tests showed that 95 to 100% of chickens vaccinated either in ovo or

lenge with various IBDv strains: the USDA (STC)

1. Introduction

Marek’s Disease (MD) and Infectious Bursal Disease (IBD), also called Gumboro disease, are the two most common immunosuppres-

ect the poultry in-dustry. MD is a common lymphoproliferative disease caused by a herpesvirus (Marek’s Dis-ease virus or MDv). Control of Marek’s disease has been achieved in the poultry industry since the 1970’s with the large-scale use of turkey herpesvirus (HVT) vaccines. Infectious bursal disease is a highly contagious infection of chickens caused by a birnavirus (IBDv) that destroys lymphocytes in the bursa of Fabricius

rst recognised more cant

economic losses in the poultry industry world-wide. In the late 1980’s a very virulent strain of

ocks in Europe and rapidly spread across the globe.

old, depending on their level of maternal im-munity against the disease. The clinical form of IBD usually occurs in chickens from 3 to

increase of mortality rate. The most frequent and economically important form of the dis-ease is subclinical and occurs in chickens less

signs of disease, but experience permanent and severe immunosuppression, reduced an-tibody response to vaccination and increased susceptibility to concurrent or secondary in-fections.

2.1. IBD vaccination,

A new vaccine, VAXXITEK HVT + IBD, combines the advantages of a live vaccine against IBDv without its safety problems and allows for ear-ly vaccination against both MD and IBD viruses (including classic, variant and very virulent IBD strains).

Early protection of chicks is key in prevent-ing IBD; this can be achieved through passive protection which is obtained by vaccinating breeding hens with inactivated IBDv vaccines. Maternal antibodies (MDAs) are transmitted to the progeny through the egg yolk to provide

life, and then titres decline. Protection against IBDv must then be maintained by administer-

ed live vaccines (MLVs).

However, MDA levels are highly variable cacy

and safety of MLVs remains an unsolved is-

the time of vaccination neutralize the vac-cine virus, chicks are generally vaccinated at

sub-protective levels. Then, approximately

to develop minimal protective titres, leaving an immunity gap between approximately 15

susceptible to IBD.

Various MLVs have been developed and clas- ed as “mild”, “intermediate” and “hot” IBD

c ca-

cy in the presence of anti-IBDv MDAs is poor. Protection provided by “intermediate” and “hot” vaccines is much higher, but these vac-cines retain some pathogenicity: they induce bursal lesions (2).

Co-administration of live MD and IBD vaccines as early as possible (ie. in day-old chicks or in ovo) has been proposed in order to induce early protection against both immunosup-pressive diseases, however this approach has

cacy prob-

2.2. VAXXITEK HVT+IBD:

VAXXITEK HVT+IBD is a live vector vaccine in which turkey herpesvirus (HVT), the most widely used MD vaccine on the market, is used as a vector expressing an IBDv antigen (VP2) (3). The HVT vaccine is well-known to be safe and poorly sensitive to interference from MDAs. VP2 is one of the major structural pro-teins of the virus, and the major host-protec-tive antigen to IBDv, containing at least three independent epitopes responsible for the in-duction of neutralizing antibodies.The vector vaccine strain is obtained by inser-tion of the IBDv VP2 gene from the Faragher 52/70 strain into the HVT virus. Its expression during vector replication triggers an immune response that protects against all types of IBDv strains (classic, variant and very viru-lent strains) (8). Since no IBDv gene respon-sible for bursal lesions is present in the vector, VAXXITEK HVT+IBD is safe, and can be admin-istered by subcutaneous injection in 1-day-old SPF chicks or by the in ovo route during trans-fer from setters to hatchers in the hatchery,

No visible gross pathological changes or sig- cant microscopic lesions of the bursa have

of 1-day-old chicks (2).

®VAXXITEK is a registered trademark of Merial in the United States of America and elsewhere.- 2 - - 3 -

cacy and safety.

isolate, the homologous Faragher 52/70 strain, the French vvIBDv strain (91168), a vvIBDv

eld isolate and a US variant E strain. Protection was evaluated either by observ-

(STC), by scoring microscopical lesions of the bursa (52/70 and 91-168), by measuring the bursa lesion score (Italian isolate) or by mea-

3.4.

3.1. Preventing the immunity gap

protectionSince VAXXITEK HVT+IBD only triggers the expression of the IBDv VP2 gene, it does not

express any gene responsible for IBDv patho-genicity: it does not induce bursal lesions in contrast to conventional MLV vaccines, even those with intermediate strains.Several experimental studies have shown that

the integrity of the bursa of Fabricius, the main target of IBDv. After challenge with various IBDv strains, bursal characteristics of vaccinat-ed broilers and pullets (size, weight, presence of microscopic or gross lesions) have been shown to be unchanged or better than those of unvaccinated birds or birds vaccinated with

Table 2a – Protection provided by vaccination of broilers with VAXXITEK HVT + IBD against experimental challenge (adapted from Goutebroze et al, 2003).

Experimental conditions

Protection against challenge with the vvIBDV 91-168 strain Broilers Challenge at 3 weeks of age

20 broilers 20 broilersChallenge at 6 weeks of age

VAXXITEK HVT + IBD (at 1 day of age)

VAXXITEK HVT + IBD yes 0/15 0/15 “Intermediate” vaccine A yes 2/15 2/15 “Intermediate” vaccine B yes 2/15 2/15 “Intermediate plus” vaccine C yes 2/15 1/15 Unvaccinated, challenged yes 15/15 2/15 Unvaccinated, unchallenged no 0/15 0/15

Full protection Full protection Antibody titre (maternal) = 1:8910 Antibody titre = 1:1 890 Controls

Antibody titre = 1:18

Experimental Persisting plateau of high levels of conditions seroneutralizing anti-IBDv antibodies reached Bublot et al, 2007 Broilers at about 6 weeks of age Field Active immune response at 3-4 weeks of age / conditions immunity gap in control birds vaccinated with a Le Gros et al, 2009 registered attenuated intermediate IBD vaccine Broilers & Field Active and strong anti-VP2 response observed Prandini et al, 2008 pullets conditions from 15 days of age

assi et al, 2008).

Pullets Italian strain at 6 weeks of age of IBD

Table 3 – Broad protection and preserved bursa integrity upon vaccination with VAXXITEK HVT+IBD.

Challenge strain Parameter evaluated Results Reference Broilers Size of bursa of Fabricius et al, than than unvaccinated controls 2003 SPF Presence of No microscopical lesions (lesions Bublot et al, 2007 microscopical lesions in 70% of controls) SPF STC strain Bublot et al, 2007 bursal lesions challenge, no matter the time of challenge Bursa-to-body weight Higher bursa-to-body weight ratio SPF variant E strain ratio 10 days after challenge when compared Bublot et al, 2007 to unvaccinated challenged controls Pullets isolate score 11 days after challenge, compared to birds Massi et al, 2008 vaccinated with MLV strains

vvIBD 91168 strain

®VAXXITEK is a registered trademark of Merial in the United States of America and elsewhere.

Bursal

Trial Immunity Reference

30

30%30%

Number 1

MER IAL TECHNICAL NE WSLET TER

eld infection

4. Improved performance with VAXXITEK HVT+IBD vaccination

1. Atienza JC, Nagera AJ, Martinez PO, Baysac ND, Castillo MT, Damaso VR, Lemière S. Evaluation of a herpesvirus of turkey vector vaccine inducing protection against infectious bursal and Marek’s diseases (VAXXITEK® HVT+IBD) under Philippines

Poultry Congress, Brisbane, Australia. 2008. Article wpc0801684, 9 p.

Use of a vectored vaccine against infectious bursal disease of chickens in the face of high-titred maternally derived antibody. Journal of Comparative Pathology, 2007;137:81-84.

3. Darteil R, Bublot M, Laplace E, Bouquet JF,

recombinant viruses expressing infectious bursal disease virus (IBDV) VP2 immunogen induce

protection against an IBDV virulent challenge in chickens. Virology, 1995;211:481-490.

Menendez A, Ruiz H et al cacy in broiler chickens in Latin America of vHVT-013, a Marek’s HVT vector vaccine expressing VP2 in infectious bursal disease virus. Oral presentation and abstract at the 15th congress of the World Veterinary Poultry Association, 2007; p199.

cacy of a recombinant vaccine HVT-VP2 against Gumboro disease in the presence of maternal antibodies. British Poultry Science, 2003;44:824-825.

6. Le Gros F-X, Dancer A, Giacomini C, Pizzoni L, cacy trial of

a novel HVT-IBD vector vaccine for 1-day-old broilers. Vaccine, 2009;27:592-596.

7. Lemière S. Marek’s virus vector vaccines inducing protection against Marek’s disease and infectious

abstract at the 8th International Marek’s Disease Symposium, Townsville, Australia. 2008. p75.

8. Massi P, Tosi G, Fiorentini L. Experimental challenge trial with a «very virulent» strain of Infectious Bursal Disease virus (vvIBDV) in commercial pullets vaccinated with an IBD vectored vaccine or with

International, November 2008;50-57.

9. Prandini F, Bublot M, Le Gros F-X, Dancer A, Pizzoni L, Lamichhane C. Assessment of the immune response in broilers and pullets using two ELISA lits after in ovo or day-old vaccination with a vectored HVT+IBD vaccine (VAXXITEK HVT+IBD). Zootecnica International, September 2008;40-50.

References

- 4 -

ocks is critical for as- cacy and antibody per-

eld infections that could have dramatic consequences. However, classical IBD ELISA tests do not easily allow for

erentiation between infected chickens and chickens vaccinated with MLVs. This is a prob-lem, particularly when bursal lesions are ob-served. A way to distinguish vaccinated from infected birds is to perform RT-PCR on IBDv strains responsible for the bursal lesions.

With the use of the VAXXITEK HVT+IBD vac- erentiate susceptible,

immunised and infected chickens on the basis of the anti-IBDv antibody response obtained by a test that uses two ELISA kits: the ProFLOK® IBD Ab test kit and the ProFLOK® IBD Plus Ab test kit. The IBD Ab test kit detects antibod-ies mainly against the VP3 antigen, present in

ed live vaccine viruses, but not in the VAXXITEK HVT+IBD vac-cine; the IBD Plus Ab test kit detects more spe-

cally antibodies raised against the VP2 an- eld and

vaccine viruses. This test kit is very sensitive and highly correlates with the virus neutraliza-

ects the protection against IBDv.

eld to monitor the appearance of protective antibodies after vaccination, with no risk of interference with infection-induced antibodies, and to show the absence of an immunity gap (6).

This approach has been successfully used in ocks in several

countries (France, Italy, Hungary) and allowed erentiation of chickens vaccinated

with VAXXITEK HVT+IBD from IBD-infected chickens, while chickens vaccinated with MLVs could not be distinguished from infected chickens (9).

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MERIAL - 29, avenue Tony Garnier, 69007 LYON - FRANCETél.: 33 (0)4 72 72 30 00Fax: 33 (0) 72 72 30 69

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Figure 2 – Mortality monitoring - Philippines trials

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Farm1VAXXITEK HVT+IBDFarm2VAXXITEK HVT+IBDFarm3VAXXITEK HVT+IBDFarm1ControlFarm2 ControlFarm3 Control

Figure 3 – Feed conversion index monitoring - Philippines trials

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Table 4 – Return on investment following vaccination with VAXXITEK HVT+IBD (adapted from Atienza et al, 2008)

Farm 1 Control VAXXITEK Control VAXXITEK ControlVAXXITEK

HVT+IBD HVT+IBD HVT+IBD Average daily gain (g) 48.49 48.25 37.52 35.57 50.33 47.81 European Performance index 287.25 261.44 156.72 124.30 240.27 190.11 Feed cost per bird (US $) $1.19 $1.31 $1.23 $1.28 $1.50 $1.69 Computed cost advantage per bird (US $) $0.13 $0.19 $0.27

4.1. Mortality and bursal protection eld performance of VAXXITEK HVT+IBD

eld trials eld trial in the Philippines

found only low grade bursal lesions post-vacci- rming that the VAXXITEK HVT+IBD

vaccine is safer than conventional vaccines in ocks vac-

cinated with VAXXITEK HVT+IBD were better protected against naturally occurring infection

ocks vaccinated with classical IBD vaccines: no clinical IBD was ob-served in these historically positive farms after vaccination with VAXXITEK HVT+IBD (1).

eld trials conducted in the Philippines and in Latin America, where classical, vvIBD and variant strains have been reported, mortality in broiler chickens vaccinated with VAXXITEK HVT+IBD was found to be much lower than in control birds vaccinated with MLVs (1,4). In the Philippines trial, bursa size, bursa weight and bursa-to-body weight ratio were found to be higher, and bursal lesion scores lower,

ocks vaccinated with VAXXITEK HVT+IBD ocks vaccinated with classical IBD

ocks vaccinated with conventional IBD vaccines (1) (Figure 2).

4.2. Growth performanceVAXXITEK HVT+IBD contributes to the devel-opment of a strong immune system and a de-creased risk of respiratory problems noticed

eld trials. Immune integrity results in ock,

as energy from feed is utilized for growth rather diseases. In broiler production,

an improvement in production performance t.

Growth parameters of VAXXITEK HVT+IBD birds eld have consistently been

found to be better than those of control groups with higher mean body weight, lower feed conversion ratio and lower mor-tality (4). In the Philippines trial, both lifetime average live weight and feed conversion ratio were

ocks vaccinated

4.3. Return on investment eld trials conducted in Latin

America (Venezuela, Peru and Brazil), the use of VAXXITEK HVT+IBD resulted in increased productivity and economic ben-

ts (Fernandez et al, 2007). The Philippines trial showed that, in practice, the use of VAXXITEK HVT+IBD in farms translates into a higher average daily gain, a higher European Performance Index (EPI) and lower feed cost per bird, compared to the use of classical IBD vaccines. This data provides evidence that the use of VAXXITEK HVT+IBD is cost-

ective, as shown by a com-puted cost advantage per bird observed in all study farms. (1) (Table 4).

Editorial

ective against classic, very virulent and variant IBD viruses, and can be used in most rst launched in 2006 in Brazil; it is now used across the globe,

rst published the preliminary work on the HVT IBD vector vaccine in 1995. Interest in the vaccine increased c journals and presentations at international avian congresses around 2003.

ts of using VAXXITEK HVT+IBD have come out. Studies have also been published on diagnostic tools for distinguishing birds vaccinated with VAXXITEK HVT+IBD from infected birds, which can be used to monitor the immune response to vaccination.

We hope that you enjoy reading VAXXITEK NEWS and invite you to discover and read our published papers

Stéphane LEMIÈREAvian Global Technical Director

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