- 1 - VAXXITEK™ is a registered trademark of Merial in the United States of America and elsewhere. - 1 - VAXXITEK™ is a registered trademark of Merial in the United States of America and elsewhere. This VAXXITEK® NEWS n°5 will provide scientific information on the HVT-IBD vector vaccine VAXXITEK HVT+IBD of Merial used in all continents and against all pathotypes of infectious bursal disease (IBD) or Gumboro disease. The idea is to review all existing published material in order to extract the results of all experiments of clinical study of protection against IBD challenge published since the registration of the vaccine in the United States of America and in the European Union, and then elsewhere, during the mid-2000ies. Diversity of IBD virus strains from the different parts of the world, ancient classical, more recent very virulent and variant strains of IBD virus have been successful to perform challenge models of IBD with the expected clinical signs of bursa damage and its consequences in vivo, and of course to demonstrate the protection induced by the vaccination with the vector vaccine VAXXITEK HVT+IBD. We hope that you enjoy reading VAXXITEK NEWS n°5 and invite you to discover and read the universal IBD protection when using VAXXITEK HVT+IBD. Dr. Stephane LEMIERE Dr. Francisco Javier ROJO BARRAÑON Avian Global Technical Director NOLA Technical Director Merial S.A.S. Merial México S.A. de C.V.
Transcript
- 1 -VAXXITEK™ is a registered trademark of Merial in the United States of America and elsewhere.
- 1 -VAXXITEK™ is a registered trademark of Merial in the United States of America and elsewhere.
This VAXXITEK® NEWS n°5 will provide scientific information on the HVT-IBD vector vaccine VAXXITEK HVT+IBD of Merial used in all continents and against all pathotypes of infectious bursal
disease (IBD) or Gumboro disease. The idea is to review all existing published material in order to extract the results of all experiments of clinical study of protection against IBD challenge published since the registration of the vaccine in the United States of America and in the European Union, and then elsewhere, during the mid-2000ies. Diversity of IBD virus strains from the diff erent parts of
the world, ancient classical, more recent very virulent and variant strains of IBD virus have been successful to perform challenge models of IBD with the expected clinical signs of
bursa damage and its consequences in vivo, and of course to demonstrate the protection induced by the vaccination with the vector vaccine VAXXITEK HVT+IBD.
We hope that you enjoy reading VAXXITEK NEWS n°5 and invite you to discover and read the universal IBD protection when using VAXXITEK HVT+IBD.
Dr. Stephane LEMIERE Dr. Francisco Javier ROJO BARRAÑON
Avian Global Technical Director NOLA Technical Director Merial S.A.S. Merial México S.A. de C.V.
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2.3. Variant IBD viruses
Cases occurred in North America in the years 1980 at the same time, and were primarily described in the USA [5]. They spread later to South America, and more recently probably to Eurasia. Bursa atrophy is the main manifestation of the infection. Field conditions signs of immunosuppression with decreased performances of growth are mainly noted in broilers.
3. Criteria to assess clinical protection against IBD virus infection
Clinical signs, mainly for vvIBD challenge, may be monitored during a virus challenge study. Bursa size and weight may be recorded, as well as bursa to bodyweight ratio, a more precise measure of the bursa atrophy taking into account the organ size and weight inter individual variability, whatever the pathotype of IBD virus to use. Bursa lesions may also be recorded using histopathological lesion technique.
3.1. Protection against clinical signs
Mainly vvIBD virus challenges originate clinical signs, and especially in layer type birds. Main observations are:
mortality, mainly in layer type birds,
drowsiness, ruffl ed feather,
poor external aspect,
detection of IBD virus antigen (s)
or viral genetic material in the
bursa of Fabricius in dead birds.
of the primary lymphoid organ, the bursa of Fabricius [3], and then regularly described on almost all places on earth. It was identifi ed as one of the major threat to the poultry industry. Layer type genetics has been proven being more susceptible to IBD than the broiler type. IBD infections may be leading to either clear IBD disease with clear clinical signs and somehow mortality. There is also a more silent form of the disease, more related to immunosuppression. From classic to very virulent strains, an increased mortality rate was the main criterion for diff erentiation [4]. Variant strains trend to escape antigenically from the rest of the virus strains, and are mainly immunosuppressive [5].
2.1. Classical IBD viruses
Mainly bursitis associated with clinical signs of drowsiness, and decrease of performances in fi eld conditions due to immunosuppression is described. Mortality may occur, and hemorrhage in muscles, as the most visible signs. The main target of the virus is the lymphoid organ structure [6].
2.2. Very virulent (vv) IBD viruses
First cases were described in Europe from the decade 1980 [7], and elsewhere, including recently in North America [8]. Clear clinical signs of hemorrhage in the bursa, the muscles, are noticed, with a higher mortality rate than with classic IBD infection.
1. Introduction
The objective of this newsletter is to review the results of the protection induced by the HVT-IBD vector vaccine VAXXITEK HVT+IBD against diff erent IBD virus challenges. All published material on VAXXITEK HVT+IBD and referring to protection against an IBD virus challenge was reviewed. First publication of such results occurred in 2003 [1].The vector vaccine strain vHVT013-IBD [2] VAXXITEK HVT+IBD has been used since 2006 in the Americas, Asia, Africa, and Europe. Vaccination against Marek’s disease, as a HVT native virus can initiate, and against IBD represents the immune foundation vaccination program to be used at the hatchery. Clinical protection against IBD has been demonstrated with the HVT-IBD vector vaccine in all types of chicken species based type of production, broilers for meat production, layers for egg production, all over the world. The reasons of such a wide use of the HVT-IBD vector vaccine are analyzed in this bibliographical review.
2. IBD virus variability in pathogenicity
Infectious bursal disease (IBD), serotype 1,virus, was recognized in 1970 as a specifi c disease at the origin of lesions
VAXXITEK™ is registered trademark of Merial in the United States of America and elsewhere.
Universal protection against infectious bursal disease (IBD) induced by the vector vaccine VAXXITEK HVT+IBD
SummaryClinical protection against all pathotypes of the serotype 1 infectious bursal disease virus is induced, from the classical viruses to the very virulent and the variants, by the HVT-IBD vector vaccine VAXXITEK HVT+IBD. Clinical protection means protection against clinical signs of the disease, mainly with the very virulent form, mortality, hemorrhage, stringent bursa atrophy, as well as protection against immunosuppression in the variant forms of the disease. Such clinical protection and therefore protection against the negative consequences of immunosuppression, poor vaccine take, occurrence of intercurrent diseases, and huge negative impact on production performances is uniquely obtained with a vector vaccine HVT-IBD vaccination that allows early onset of immunity, either in ovo at transfer time around 18 days of embryonation, or at day old in the hatchery, in presence of IBD virus maternally-derived antibodies.
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3.2. Protection against bursa
atrophy
All types of challenge studies may use monitoring of bursa size and/or weight. The measurement is the calculation of the bursa to bodyweight ratio on freshly collected organs at necropsy. One way to express the results may be based on bursa as defi ned for example:
body weight ratio (B/BR) [9], bursa
weight (g) / total bodyweight (g),
bursa index (BI) [10], bursa
weight (g) x 1000 / body weight (g).
3.3. Protection against bursa
lesions
All types of challenges studies may use monitoring of bursa lesions. The measurement is the bursa lesion rating performed on histopathological examination of bursa. One way to express the results is based on the mean severity index (MSI), severity of bursa lymphoid tissue lesions is scored from 0 to 4 on the basis of lymphoid necrosis and/ or lymphocytic depletion [9]:
0 = less than 5 % of the lymphoid follicles (per fi eld) aff ected,
1 = 5 to less than 25 % of the lymphoid follicles (per fi eld) aff ected,
2 = 25 to less than 50 % of the lymphoid follicles (per fi eld) aff ected,
3 = 50 to less than 75 % of the lymphoid follicles (per fi eld) aff ected,
4 = more than 75 % of the lymphoid follicles (per fi eld) aff ected.
4. Clinical protection induced by VAXXITEK HVT+IBD
Review of results of all published protection studies in laboratory controlled conditions using the HVT-IBD vector vaccine worldwide provides a demonstration of the universal protection against IBD.
4.1. Classical IBD viruses
Protection against classic IBD virus challenges has been studied since the time of development of the vaccine [2] (Table 1). Either in ovo or day-old sub-cutaneous routes have been both tested providing clinical protection against classic IBD challenge [2].
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Most of the experiments were performed in specifi ed-pathogen free chickens. Protection against IBD virus challenges were using homologous to the vHVT013-IBD vector vaccine VAXXITEK HVT+IBD virus, as the Faragher 52/70 first isolated in the United Kingdom [11]. Layer pullet type of birds was protected against Faragher 52/70 challenge [12]. Further published studies were mainly about hatchery vaccination program validation. VAXXITEK HVT+IBD was shown compatible with live Newcastle disease and infectious bronchitis Mass strain vaccines sprayed at day-old using a Faragher 52/70 challenge model [13]. Protection against STC United States originated challenge strain was also demonstrated [14]. That model, as well a Winterfield challenge model were selected to assess protection against challenge in the context of concomitant injection at day-old of VAXXITEK HVT+IBD and a Newcastle disease inactivated vaccine in oil emulsion [15] & [16].
4.2. Very virulent (vv) IBD viruses
Protection against very virulent (vv) IBD virus challenges has also been studied since the time of development of the vaccine [2] (Table 2). Either in ovo or day-old sub-cutaneous routes have
been both tested providing clinical protection against vv IBD challenge [2]. Not only SPF chicken challenges have been performed so far, but also broiler [1] and layer pullet [16] challenges gave expected results of protection in VAXXITEK HVT+IBD vaccinates [17]. Two French isolates were used for studies, 89-163 and 91-168 isolates from the ANSES national reference laboratory. 77165 isolate from IZ Forli institute in Italy served as challenge strain for layer pullet protection studies [18], and broiler protection studies [19]. Interestingly VAXXITEK HVT+IBD injected either in ovo or at day-old showed protection against Brazilian molecular group 11 vvIBD virus isolate based challenge [11]. A study of protection against vvIBD challenge of progeny born to VAXXITEK HVT+IBD based vaccinated parents and vaccinated in ovo with VAXXITEK HVT+IBD confirmed the interest of the vector vaccine used as a primer in meat breeders, and of the early onset of immunity and induced protection against vvIBD before the waning of the protective maternally-derived antibodies [20] & [21].
IBD virus challenge strain Type of birds Vaccination Reference
Faragher 52/70 UK
SPF chickensIn ovo & day-old sub-cutaneous injection
Fernandez R al, 2006
SPF chickens Cruz-Coy J al, 2006
Layer pullets Day-old sub-cutaneous injection Icochea E al, 2007
SPF chickensDay-old sub-cutaneous injection
+ live Newcastle disease & infectious bronchitis vaccine sprayJay ML al, 2009
STC USA
SPF chickens In ovo & day-old sub-cutaneous injection Bublot M al, 2007
SPF chickens Day-old sub-cutaneous injection Perozo F al, 2010
IBD virus challenge strain Type of birds Vaccination Reference
91-168 ANSES France
Broilers Day-old sub-cutaneous injection Goutebroze S al, 2003
SPF chickens In ovo & day-old sub-cutaneous injection Bublot M al, 2007
SPF chickensDay-old sub-cutaneous injection Le-Gros FX al, 2009
Broilers
89-163 ANSES France
SPF chickens In ovo injectionRautenschlein S al, 2009
Layer pullets Day-old sub-cutaneous injection
Meat breeder progeny* In ovo injection Lemiere S al, 2013
77165 Italy
Layer pullets
Day-old sub-cutaneous injection
Prandini F al, 2008
Layer pullets Massi P al, 2008
Broilers Le-Gros FX al, 2009
GM11 BrazilSPF chickens
In ovo & day-old sub-cutaneous injectionFernandez R al, 2006
SPF chickens Cruz-Coy J al, 2006
*Progeny born to VAXXITEK HVT+IBD based vaccination program of parents.
Table 2: VAXXITEK HVT+IBD very virulent (vv) IBD virus protection against challenge studies.
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4.3. Variant IBD viruses
Protection against variant IBD virus challenges has also been studied since the time of development of the vaccine [2] (Table 3). Either in ovo or day-old sub-cutaneous routes have been both tested providing clinical protection against variant IBD virus challenge [2]. Mainly variant E Delaware challenge model has been successfully used so far for protection studies [22] & [23]. Clinical protection induced by VAXXITEK HVT+IBD was fully demonstrated, emphasizing the correct choice of the Faragher 52/70 IBD protective VP2 gene to be inserted into the HVT vector virus. This strain was isolated at the fi rst days of Gumboro disease and may be considered as a progenitor of all existing IBD viruses in the world. The variant E Delaware challenge test was also used for validation of induced protection of VAXXITEK HVT+IBD in the context of concomitant vaccination with an oil emulsion inactivated Newcastle disease vaccine at day-old at the hatchery [16] & [24]. A study of protection against three USA variant challenge strains,
Delaware E, AVS-SU and AVS-DL, of progeny born to VAXXITEK HVT+IBD based vaccinated parents confi rmed the interest of the vector vaccine used as a primer in meat breeders, and of the passive protection against these variant IBD strains before the waning of the protective maternally-derived antibodies [25] & [26].
5. Conclusion
IBD infections result in lesions of the bursa of Fabricius of different severity [3], [4] & [5], and therefore the immune system function is highly and negatively impacted. Most of live attenuated IBD vaccines may cause bursal atrophy and immunosuppression Poor response to other vaccinations
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2. Bublot M, Pritchard N, Le Gros F-X, Goutebroze S. 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. Hitchner SB. Infectivity of infectious bursal disease virus for for embryonating eggs. Poultry Science, 1970; 49:511-516.
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6. Cheville NF. Studies on the pathogenesis of Gumboro disease in the bursa of Fabricius, spleen and thymus of the chicken. American Journal of Pathology, 1967;51:527-551.
7. Chettle NJ, Stuart JC, Wyeth PJ. Outbreak of virulent infectious bursal disease in East Anglia. Veterinary Record, 1989;125:271-272.
8. Jackwood DJ, Sommer-Wagner SE, Stoute ST, Woolcock PR, Crossley BM, Hietala SK, Charlton BR. Characteristics of a very virulent infectious bursal disease virus from California. Avian Diseases, 2009;53:592-600.
9. Sharma JM, Dohms JE, Metz AL. Comparative pathogenesis of serotype 1 isolates of infectious bursal disease virus and their eff ect on humoral and cellular immune competence of specifi c-pathogen-free chickens. Avian Diseases, 1989;33:112-124.
10. Lucio B, Hitchner SB. 1979, Infectious bursal disease emulsifi ed vaccine: Eff ect upon neutralizing-antibody levels in the dam and subsequent protection of the progeny. Avian Diseases, 1979;23:466-478.
11. Cruz-Coy J, Oliveira C, Pereira J, Ambrosino F, Gaudenci A, Le-Gros FX, Pritchard N. Effi cacy of a Turkey Herpesvirus (HVT-MDV serotype-3)-Infectious Bursal Disease (IBD) Vaccine, Live HVT Vector, IBD-VP2, Administered in ovo and to One-Day-Old SPF Chickens.Poster presentation. American Association of Avian Pathologists convention, Hawaii, United States of America. 2006; p135.
12. Icochea E, Talavera B, Davila E, Gonzalez R, Guzman J, Rivera H. Effi cacy of a vectorized commercial vaccine against Infectious Bursal Disease in Layers. Abstract. Association of the American Avian Pathologists Convention, Washington D.C., United States of America, 2007; p60.
13. Jay ML, Bizzini S, Duboeuf M, Goutebroze S, Le-Gros FX. Compatibility of a novel vector vaccine HVT-Gumboro with Newcastle and infectious bronchitis vaccination at one day of age. Abstract. 16th congress of the World Veterinary Poultry Association, Marrakesh, Morocco, 2009; p341.
14. Perozo F, Villegas P, Mavarez Y, Fernandez R, Cuz J. Effi cacy of a Recombinant Turkey Herpesvirus Expressing the Viral Protein 2 of the Gumboro Disease Virus Against an Experimental Challenge. Vez REV-LUZ, 2010;20:132-137.
15. Wong YS, Saint-Gerand AL, Liao GA, Toh PL, Lim CC, Lemiere S. Compatibility of VAXXITEK HVT+IBD with inactivated in oil emulsion Newcastle disease (ND) vaccine administered by sub-cutaneous route at day old using a challenge against infectious bursal disease virus (IBDv) and using serology. Oral presenta-tion. 16th congress of the World Veterinary Poultry Association, Marrakesh, Morocco, 2009; p167.
16. Lemiere S, Fernandez R, Pritchard N, Cruz-Coy J, Rojo F, Wong SY, Saint-Gerand AL, Gauthier JC, Perozo F. Concomitant Turkey Herpesvirus–Infectious Bursal Disease Vector Vaccine and Oil-Adjuvanted Inactivated Newcastle Disease Vaccine Administra-tion: Consequences Compatibility of Turkey Herpesvirus–Infec-tious Bursal Disease. Avian Diseases., 2011; 55:642-649.
17. Rautenschlein S, Simon B, Jung A, Pöppel M, Prandini F, Lemiere S. Protective effi cacy of VAXXITEK HVT+IBD in com-mercial layers and broilers against challenge with very virulent infectious bursal disease virus. Oral presentation. 16th congress of the World Veterinary Poultry Association, Marrakesh, Mo-rocco, 2009; p166.
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20. Lemiere S, Gauthier J.C., Kodjo A., Vinit L., Delvecchio A., Prandini F. Evaluation of the Protection against Infectious Bur-sal Disease (IBD) Challenge in Progeny Born to Parents Having Received a Vaccination Program Using a Herpesvirus of Turkey-Infectious Bursal Disease (HVT-IBD) Vector Vaccine. World Jour-nal of Vaccines, 2013; 3:46-51.
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22. Perozo F, Villegas P, Fernandez R, Cruz J. Protection against variant strains conferred by the recombinant HVT-IBDV vaccine VAXXITEK. Oral presentation. 58th Western Poultry Conference, Sacramento, CA, United States of America. 2009; p85-86.
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24. Fernandez R, Cruz J, Rojo F, Garcia H, Baudon J, Pritchard N. Effi cacy of Vaxxitek® and a commercially available oil-emulsion NDV vaccine administered simultaneously by the subcutaneous route using the Accuvac® Twinshot or the Oneshot machines to vaccinate day-old commercial broilers. Abstract. 60th West-ern Poultry Disease Conference, Sacramento, United States of America, 2011; p73-74.
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26. Montiel E, Pritchard N, Cruz J, Katigbak E, Wilcox M, Wilson J. Vaccination of broiler breeders with a herpesvirus of turkey-infectious bursal disease virus (IBDV) vector vaccine: serocon-version and progeny challenge studies. Abstract. American Association of Avian Pathology Symposium, Atlanta, United States of America, 2010; p102.
27. Müller H, Mundt E, Eterradossi N, Islam MR. Current status of vacines against infectious bursal disease. Avian Pathology, 2012, 41:133-139.
and occurrence of intercurrent infections may be a consequence of such vaccination [27]. Full protection against vvIBD and variant IBD may be incomplete with such vaccines [27]. The compromise between a possible early immunization and the overpassing of maternally-derived IBD antibodies is obtained with the HVT-IBD vector vaccine [1].
