Gumboro Disease, more properly called Infectious Bursal Disease (IBD), is one of the most important viral diseases of chickens. The virus responsible for this condition (IBDV) can be found in almost all farms and countries.
Many studies have already been conducted on this disease but more are still needed to better understand the consequences of the genetic and antigenic variations detected in the virus, the mechanisms of infection as well as how to better protect the chickens.
The objective of this presentation is to summarize, in a few pages, the key points of controlling the disease utilizing vaccines. Because of this format constraint, the presentation will be selective and simplified.
The causative virus (IBDV)
- Extremely resistant in the environment, thus explaining the persistence of the disease in contaminated premises as well as its wide geographic spread.
- Highly variable:
- from an antigenic point of view (the viral protein VP2, which is also the main support for immunogenicity, allows the differentiation between « classical » and« variant » strains)
- from a pathogenic point of view (IBDV strains are also classified as poorly virulent, classical virulent and very virulent).
The virulence factors are not fully identified.
Little is known regarding the heterogeneity of the IBDV strains present in a given region. However, some investigation conducted in the USA demonstrated that at least 5 clearly different genetic types could be isolated from a panel of 30 farms, belonging to the same poultry producing company, and spread in a geographical area of about 100 km2.
The consequences of infection with IBDV
The consequences of infection with IBDV vary according to the type and virulence of the virus, the type of chickens (light breeds with slow growth are more susceptible than heavy breeds), the challenge dose and the age at challenge. These consequences can include: mortality, immunodepression, technical and economical losses, or no easily detectable consequences.
The objectives of vaccination against IBDV
The main objectives of vaccination against IBD are to reduce the clinical signs, lesions and economical consequences associated with infection by IBDV. Until now, nothing is expected regarding prevention of infection, reduction of the re-excretion of the challenge virus, or eradication of the disease.
Humoral immunity is considered the most important factor to neutralize IBDV and protect chickens.
Vaccines available to prevent Gumboro disease
Inactivated type IBD vaccines
Most of the inactivated IBD vaccines are made from whole IBD virus produced either in embryonated eggs, cell cultures, or in living chickens whose bursas are collected a few days after inoculation. Harvested IBDVs are inactivated, and then put in suspension in an oily emulsion that plays the role of adjuvant.
Sub-unit inactivated vaccines made from the VP2 antigen produced in an expression system (yeast) have also been made commercially available.
The quality of inactivated vaccines varies according to their antigen content (antigenic mass), the inactivation process, the adjuvants, the formulation as well as the way they are prepared.
They are presented as oily liquid emulsions and must be injected (IM or SQ).
Inactivated IBD vaccines are mostly used to stimulate the production of antibodies (humoral immunity) in breeders, and to passively protect their progeny.
Live attenuated type IBD vaccines :
Live attenuated vaccines contain naturally or artificially attenuated live viruses propagated in embryonated eggs or cell cultures.
There are multiple types of live attenuated IBD vaccines and they vary according to the virus titre per dose and the nature and degree of attenuation of the selected IBDV strain. The stronger the attenuation, the higher the susceptibility to interference with MDA (Maternally Derived Antibodies), the lower the spreading capacity, the more difficult the administration, and the lower the efficacy against "very virulent" field strains.
Due to variable titre and attenuation levels, these vaccines are classified as i) "mild" strains (almost no longer used nowadays, because of a too high degree of attenuation), ii) "intermediate" strains, iii) "intermediate plus" and iiii) "hot" strains that are close to the field virus.
Live attenuated vaccines are presented as freeze dried vaccines, and need to be administered preferably using the drinking water method of vaccination (the eye , intra nasal as well as the spray or the injection method of administration can also be used, but have revealed less efficacious under conditions of field use).
After a proper "take" of the vaccine, immunity seems to be complete and protects the chickens against re-infection, even if an antigenically very different strain is used (Palya et al. 2009).
Immune complex type live IBD vaccines :
Immune complex vaccines are made by mixing, in well defined proportions, a suspension of live attenuated IBDV (produced in embryonated eggs) with specific antibodies (produced in SPF chickens) that bind to the IBDV. The complex is freeze dried after mixing and presented as an injectable preparation, to be reconstituted with a diluent before injection to day-old chicks or "in-ovo".
Because of the natural binding with specific antibodies, the live IBDV is not recognized by the immune system of the host, and also not neutralized by the MDA. After a few days or weeks of life, when most of MDA have disappeared, the vaccine virus is released from the antibody-virus complex and starts replicating, which leads to the induction of active immunity.
Replication of the vaccine starts sooner or later, depending on the initial level of MDA, but always at the perfect time. At individual level, the induced protection is similar to the one obtained with an intermediate plus type, live attenuated vaccine, administered at the optimal vaccination time. At the flock level, the resulting immunity is very homogenous.
Recombinant (vector) type live IBD vaccines:
The commercially available recombinant type live IBD vaccines are using the Herpes Virus of Turkey (HVT) as vector. This very stable and safe virus is used worldwide to prevent Marek´s disease. The gene encoding for the VP2 protein has been extracted from a "donor" IBDV and ed inside the genome of the HVT. When replicating, the HVT expresses the VP2, which induces protection in the vaccinated animal.
Since HVT (as an herpes virus) is poorly sensitive to MDA directed against itself, and circulating MDA directed against IBDV have no action against the recombinant virus (because no IBD virus is present and HVT remains mostly intracellular), vaccination can be successfully given in the presence of MDA. Interestingly, active protection does not take over from passive immunity but adds progressively to it when, at the same time, compensating for its decline.
Immunity that is induced opposes to infection, delays it, but is not always capable to prevent it, neither at the level of all follicles of the bursa, nor at the level of all birds within the same flock (Penzès et al. 2008).
The immunization strategies
Induction of passive immunity in the progeny by vaccination of the breeders.
- This strategy has been adopted by most of the poultry producing companies in most of the countries.
- It is based on hyper-immunisation of the breeding hens thanks to the successive application of live attenuated and inactivated IBD vaccines.
- The inactivated vaccines are generally produced from « classical » IBDV strains, but can also be made from « variant » strains if needed by epidemiological conditions (USA).
The objective of this strategy is to protect the progeny against early infection responsible for severe immuno-depression.
Induction of active immunity in the young chicks to take over from passive immunity.
- This strategy is routinely applied almost everywhere, except in the USA. In this country, the widespread presence of "variant" IBDV and the corresponding high risk of immuno-depression due to early infection, explain why the IBD vaccination programs rely essentially, if not exclusively, on (heavy) breeder programs.
- The main difficulty associated with this approach is the interference between live IBD vaccines and MDA that can lead to a full neutralization of the vaccine virus.
- This early vaccination in the presence of MDA can be done :
- either with (more or less) attenuated live vaccines, administered most of the time at farm by drinking water. The efficacy depends on the degree of attenuation, the quality of the administration, and mostly on the vaccination date that needs to be adapted to the hardly predictable level of MDA present in the day-old chicks. The use of serology to "calculate" an optimal vaccination time has proven to be efficacious and should be recommended.
- or with vaccines of the immune complex or vector types. These vaccines are not susceptible to interference with MDA but need to be injected. This is why they are injected at the hatchery, either by sub-cutaneous injection at day-old or in-ovo at 18 days or more of embryonic development.
The objective of this strategy is to induce active immunity to take over passive immunity and prevent late infections with IBDV, and in particular with the very virulent type of IBDV that can be so detrimental.
The immunization process
Inactivated vaccines, especially when used for boosting live vaccines, induce very high levels of antibody in the breeders (hyperimmunisation). This antibody mediated immunity is transferred to the young chick through the egg yolk and represents the main support of passive immunity. The search for high and homogenous passive protection in the progeny is the only reason to use them.
Live attenuated vaccines as well as immune complex type vaccines (that release live attenuated vaccine viruses) induce a full immunity, and their replication, if effective, seems to protect the chickens against any further field infection, including with antigenically different viruses.
Commercially available live vector vaccines (all of the rHVT-IBD type) are less understood. Experiments conducted under controlled laboratory conditions, as well as in the field demonstrate that corresponding immunity does not prevent infection with field viruses but delays the occurrence of lesions, and reduces their intensity (Gardin et al. 2010).
The monitoring of vaccination against Gumboro disease
The efficacy of vaccination against Gumboro disease can be evaluated through the reduction or prevention of clinical signs or economical losses in case of challenge.
Its effectiveness can be demonstrated by evidencing the presence of the vaccine virus in the bursa of Fabricius (in case of live attenuated or immuno-complex type vaccines), or at the level of the pulp of the feather follicles (in case of rHVT-IBD type vector vaccines - Esaki et al. 2009).
Serology, with special regards to ELISA serology, can bring very useful and very reliable information (a negative titre two weeks after vaccination indicates a vaccination failure). However, this information is not specific enough to allow differentiation between vaccination and infection by a field virus.
Administration of IBD vaccines in practice
The proper administration of live attenuated and inactivated IBD vaccines under field conditions has remained for long an underestimated problem.
The information collected after using the monitoring tools that are now available and allow for identification of the IBDVs (RT-PCR, RFLP, sequencing) has revealed how bad the situation was.
It is more than easy to demonstrate that, very often, in a given poultry producing organisation, more than 30% of the farms considered as "vaccinated" have not been actually "immunized", and it is unfortunate to realize that this percentage can easily be increased.
It is actually possible to properly vaccinate poultry, and techniques and procedures necessary to be successful are known and readily available. However, we know by experience that most of the time, improvement is transient, and this is just because to run a good vaccination is heavy and requires a free time that the farmer or the farm workers do not have.
This explains why new Gumboro vaccines that are not affected by MDA (immune-complex or vector types) and can be administered at the hatchery, either by SQ or in-ovo injection, have met a real commercial success. Despite an extra cost, and sometimes extra hatchery organization constraints, poultry production managers are keen to make the decision and the farmers do request for it.
Today, it is clear that in the near future, most of vaccinations in poultry, including vaccination against Gumboro disease, will be applied at the hatchery, because it is simpler, easier, and more efficacious, and also because new technologies are now available to develop the corresponding necessary new vaccines.
Esaki M., Sato T., Jensen L., Saitoh S., Saeki S., Fujisawa A. and Moore Dorsey K. 2009. Detection of Vectormune HVT vaccines in feather tips by real time PCR. AAAP Meeting, Seattle, USA
Gardin Y., Palya V., Sesti L. and Moore Dorsey K. 2008 - Efficacy of Infectious Bursal Disease . Virus Vaccine against various forms of the disease. AAAP Meeting, New Orleans, USA.
Gardin Y., Palya V. and Soares R. 2008 - Interest of using an antigen antibody complex IBD vaccine in the prevention of IBD. 57th WPDC / 33 ANECA, Puerta Vallarta, Mexico.
Gardin Y. 2008 - Vaccination in the hatchery : the assurance of a good start. Poultry Focus Asia. Bangkok, Thailand.
Gardin Y. and Jaquinet C. 2008 - Cevac Transmune : une nouvelle approche de la vaccination contre la maladie de Gumboro. Rencontres Internationales de Production et de Pathologie Aviaire (RIPPA), Rennes France.
Gardin Y., Moore Dorsey K. and Palya V. 2008 - Immune complex and Vector vaccines for Gumboro disease control. Vaccination 2008 Positive Action, Hannover, Germany.
Gardin Y., Ritter D., Rosenberger J., Rosenberger S., Godoy A., Esaki M., Jensen L., Eddins T., Boggan G., Palya V., and Moore Dorsey K. 2010 - Field investigations using an rHVT-IBD vaccine in U.S. broilers. AAAP Meeting, Atlanta, USA.
Palya V., Màto T., Tatar Kiss T. and Gardin Y. 2009 - Spectrum of protection provided by passive and active immunity to IBD viruses. AAAP Meeting, Seattle, USA.
Pensès Z., Horvàth T., Sombor T., Màto T., Kardi V., Süveges T. and Palya V. 2008 - HVT-IBDV-VP2 recombinant vaccines : characteristics of bursal protection following vvIBDV challenge. 8th MD symposium, Townsville, Australia.