Articles on Infectious Bursal Disease | Gumboro Prevention

Antigenic drift in variant Infectious bursal disease viruses can be explained by a single point of mutation in the VP2 protein

Adrià Martos — Fri, 30 Aug 2024 08:27:21 +0000

Outbreaks of infectious bursal disease (IBD) are still reported throughout the world despite efforts to control the disease through vaccination. Control efforts are complicated by the fact that the causative agent is subject to frequent genetic mutations, reassortment of genome segments, and genomic recombination events that can potentially increase virulence and alter antigenicity. It is known that antigenic variants of IBDV possess modified neutralizing epitopes that allow them to evade the action of maternally-derived or vaccine-induced antibodies.

Infectious bursal disease virus (IBDV) structure

IBDV is a member of the family Birnaviridae and contains a double-stranded RNA genome consisting of two segments, A and B. Segment A encodes the VP2, VP3, VP4 and VP5 proteins, while segment B encodes the protein VP1. The VP2 protein is the major host-protective immunogen of IBDV and carries all the neutralizing epitopes, some being responsible for antigenic variation (Brown et al., 1994). It also contributes to the antigenicity, tropism and pathogenicity of the virus. It forms trimeric sub-units to build the viral capsid and exhibits surface projections corresponding to the central or hypervariable region, the part of the VP2 protein most exposed to immune pressure and hence the one most prone to mutations.

Source: Expression and Characterization of Infectious Bursal Disease Virus Protein for Poultry Vaccine Development and Application in Nanotechnology (Taghavian et al. 2013).

Antigenic drift in IBDV

Antigenic drift is thought to be responsible for the formation of antigenic IBDV variant strains, due to substitution mutations in the hypervariable region of VP2 (Heine et al., 1991). Some of these amino acid mutations enable the virus to escape from neutralizing antibodies produced by vaccination with classic IBDV strains. In 2011, Daral J. Jackwood and Susan E. Sommer-Wagner published a study in which the effect of amino acids 222 and 254 on antigenicity of the variant Del-E strain of IBDV was examined.

“ Amino acids contributing to antigenic drift in the infectious bursal disease Birnavirus (IBDV) ”

The main objective was to assess whether a single point mutation could significantly contribute to antigenic drift in the Del-E strain of IBDV, allowing the virus to evade the humoral immunity induced by the original Del-E virus variant IBDV vaccine.

Methodology

Two Del-E strain viruses with different single substitution mutations (Fig 1) were obtained from a Del-E virus (strain 89/03) and their antigenic property was assessed in vivo for the first time ever reported:

Del-E-222 virus, that was identical to Del-E except for alanine at position 222.
Del-E-254 virus, generated using reverse genetics and containing an asparagine at amino acid 254.

These mutations were selected since they were observed in viruses that caused disease in commercial chicken flocks (Jackwood and Sommer- Wagner, 2005). After obtaining these mutant viruses, their ability to evade neutralizing immunity provided by parenteral vaccination using a Del-E 89/03 vaccine strain and cause disease in chickens was tested.

Results

The Del-E vaccine (89/03) was administered according to the manufacturer’s instructions and induced neutralizing and ELISA antibody titres to the virus. The immunity created by this vaccine protected the SPF chickens from disease following challenge with an antigenically homologous Del-E virus. The results of this trial were as follows:

RT- PCR: the efficacy of the Del-E vaccine was appreciably affected. The strains detected following challenge of the vaccinated birds using this real-time RT-PCR assay were Del-E-222 and Del-E-254. The fact that both challenges were capable of breaking through the vaccine immunity is strong evidence that the amino acid mutations at positions 222 and 254 in VP2 were contributing to antigenic drift.
Macroscopic lesions: the bursas from birds vaccinated with Del-E and challenged with Del-E-222 or Del-E- 254 had macroscopic lesions typical of an IBDV infection, and their bursa-body weight (B-BW) ratios were significantly smaller than the control groups.
Microscopic lesions: presence of lymphocyte depletion in the bursas. The ability of Del-E-222 and Del-E-254 to break through the immunity induced by the Del-E virus vaccination was confirmed.

Conclusions

The results supported their hypothesis that a single point mutation can significantly contribute to antigenic drift in Infectious bursal disease viruses in vivo and enhance their ability to evade immunological control efforts used in the poultry industry. Although the 222 and 254 amino acid positions in hvVP2 appear to be important for antigenic drift in Del-E variant viruses, substituting different amino acids at these sites might not have significantly altered antigenicity. Moreover, monoclonal antibody studies suggest that the 222 and 254 amino acid sites are not the only ones contributing to antigenic drift (Eterradossi et al., 1997; Letzel et al., 2007; Vakharia et al., 1994). Taken together, this information suggests that humoral immunity against IBDV has limitations when new variants emerge, and that the protective role of competitive exclusion by live vaccines at the Bursa of Fabricius might become increasingly important. In conclusion, given these findings, it is crucial to continuously evaluate the prevalence of circulating strains in specific areas and to determine whether the current vaccination programme provides effective and complete protection against them.

La entrada Antigenic drift in variant Infectious bursal disease viruses can be explained by a single point of mutation in the VP2 protein se publicó primero en Gumboro Prevention.

Reassortant very virulent IBDV in Europe. Is there a correlation between positivity on broiler farms and the type of vaccine currently used?

Adrià Martos — Thu, 14 Mar 2024 09:33:10 +0000

Infectious bursal disease virus (IBDV) has a genome consisting of two segments of RNA (Müller et al. 2003). Segment A contains the VP2 protein, which is the main host protective antigen and is responsible for causing neutralizing antibody production (Dey et al. 2019). Segment B encodes protein VP1, which also contributes to the virulence and evolution of IBDV (Yang et al. 2020). The most common classification for IBDV is based solely on segment A, but, with the emergence of novel strains produced by mutation, recombination or reassortment events, it is increasingly difficult to define them using the traditional classification method.

In recent years, a reassortant IBDV strain has been continuously reported in many European countries (Tamas Mato et al. 2020).

Genetic analysis based on the VP2 gene classified these isolates as very virulent IBDV strains (vvIBDV, Genogroup 3), while the VP1 gene was more closely related to classical attenuated IBDV strains. Likewise, sequencing reports from bursas of Fabricius (BF) at HIPRA Diagnostic Services (HIPRA Diagnos) have repeatedly identified the sequence of IBD reassortant strains (named UK2019), linked to subclinical outbreaks and characterized by immunosuppressive signs, low performance and bursal atrophy (E. Marzo et al. 2023). For this reason, a study was initiated on poultry farms in order to have an indication of the spread of this new virus in the Netherlands and to investigate whether there is a relationship between its appearance and the currently used vaccine strategy (P. Kühne et al. 2023).

Methodology

FTA card samples were taken from 66 farms producing slow-growing broilers. The farms were randomly selected and included those with different vaccination strategies:

Non-vaccinated
Recombinant HVT-IBD
Intermediate live IBDV (drinking water)
Intermediate plus live (including both drinking water and immune complex vaccines)

Seventy-six samples were sent to HIPRA Diagnos in Spain, all taken at least two weeks after the application of a Gumboro vaccine. The laboratory ran a RT PCR test, and in the case of a positive result, a nucleotide sequencing procedure was performed following the Sanger methodology. The sequences obtained were compared with both IBDV reference strains (Genbank) and field strains.

Results:

The percentage positivity for field virus UK2019 was analysed in all samples and by type of vaccine classification (Table 1):

Table 1. Overall field virus positivity and positivity by vaccine classification *A significantly lower proportion of field virus strain was detected with intermediate plus vaccines compared to non-vaccinated flocks or those vaccinated with intermediate strain vaccines (p-value = 0.001).

These results indicate that vaccines with intermediate plus live viruses seem to be the best option for the control of these new strains, probably due to the important role that protection by competitive exclusion plays in this disease. The positivity for field virus UK2019 by type of vaccine was 21.7% for the drinking water vaccines, 44.4% for the recombinant vaccines and 0% in immune complex vaccines (Fig. 1). Furthermore, 33.3% of the recombinant vaccine samples showed positivity for a Winterfield 2512 strain (probably coming from another vaccine used in previous flocks). This result indicates that the protection observed from this vaccine type could be reduced to 22%.

Fig. 1. IBDV positivity and type of strain by vaccine type.

Conclusions:

The results of this prevalence study confirmed the circulation of the new reassortant IBDV strain (UK2019) in the Netherlands and demonstrated a relationship between the positivity of the field strain and the type of vaccine used, indicating that intermediate plus vaccines, especially when in the form of immune complex vaccines, are the best option for controlling field circulation on farms producing slow-growing broilers.

La entrada Reassortant very virulent IBDV in Europe. Is there a correlation between positivity on broiler farms and the type of vaccine currently used? se publicó primero en Gumboro Prevention.

Displacing IBDV variant strains with the use of a new generation immune complex vaccine

mireiadiaz — Mon, 21 Nov 2022 12:51:39 +0000

Gumboro disease (IBDV) is one of the most important immunosuppressive diseases of chickens that causes high economic losses to the poultry industry worldwide. In recent years, several publications have described the great impact that the subclinical form of Gumboro disease has had on large South American farms where the circulation of the virus variant has been detected¹.   In Brazil, Gumboro disease was first detected in the 1970s² and although the disease was considered well-controlled after the widespread use of commercial vaccines, novel variant IBDV strains have now emerged, posing new threats to the poultry industry.   

Infectious bursal disease virus is classified into three main groups according to antigenic and virulence properties: classical virulent (cvIBDV), very virulent (vvIBDV) and antigenic variants (avIBDV)³. This last group has been recently classified into genogroups G2, G4, G5, G6, and G7 and it is distributed in specific regions around the world.   Brazilian antigenic variants (avIBDV) have been detected in flocks with mild immunosuppression and low mortality related to secondary infections, but without presenting classical signs of Gumboro disease. Of several samples analyzed in a study in Brazil⁴, 35.42% were classified as avIBDV which were previously classified as GM15 and GM16⁵. 

Objective

The objective of this study was to evaluate the efficacy of new generation immune complex (GUMBOHATCH®) in Brazilian farms where variant Gumboro virus was circulating. GUMBOHATCH® is a new immune complex vaccine against Gumboro disease that has been developed by HIPRA. This vaccine has introduced a different formulation (IgY of egg origin) and control parameters (detection of free IgY and neutralisation control) to guarantee complete coating of the IBDV vaccine virus at the time of inoculation. The result of all these new improvements is a new-generation immune complex vaccine that allows maximum potency of the vaccine to be maintained and consistent results to be obtained in the field, whilst at the same time avoiding the risk of immunosuppression.

Methodology

Number of animals: 5,390,333 chicks

Vaccination: GUMBOHATCH®

Administration route: in-ovo at 18 days of incubation

Vaccination was performed in two cycles in accordance with the instructions in the package leaflet. All chicks were located in the north-east farms of Brazil after hatching:

Cycle 1 in 80 commercial broiler farms
Cycle 2 in 81 commercial broiler farms

All farms had been previously diagnosed with an avIBDV circulation, despite the fact that a vaccination programme based on the administration of standard formulated immune complex vaccine was in place. Different safety and efficacy parameters were evaluated and monitored until the end of the rearing period (42 – 43 days of life).

15 birds/ farm at different times in each cycle
Blood: antibody titres using CIVTEST® AVI IBD (HIPRA)
Bursa of Fabricius: macro and microscopic lesions + PCR analysis + histopathology (29-33 days of age)

To evaluate the efficacy of GUMBOHATCH®, a comparison of the production results and the production cost differential from Cycle 1 (first contact of the farms with GUMBOHATCH®) vs Cycle 2 (stronger presence of the GUMBOHATCH® vaccine virus expected) was carried out.  

Results

SAFETY

No adverse reactions were observed on any of the farms regardless of the cycle.
Expected signs of replication of the vaccine virus were observed in the bursas, but no lesions correlated with the field virus circulation were detected.
Histopathology differences were observed in the bursas, with greater homogeneity of scores in Cycle 2 compared to Cycle 1 (data not shown).

EFFICACY The serology results were as expected for GUMBOHATCH® in both vaccination cycles (Cycle 1 = mean titre 6141.14; Cycle 2 = mean titre 5593.47). However, major differences were seen between the PCR results for the two cycles (Figure 1).

Cycle 1 = 28.75% of samples were positive for GUMBOHATCH®, 28.57% positive for virus variant (GM15), 28.57% were positive for both, GUMBOHATCH® + field virus and 14.28% of the samples were negative.
Cycle 2 = 100% of the samples analyzed were positive for GUMBOHATCH®.

Figure 1. PCR results as percentage positivity of the bursal samples analyzed in Cycle 1 and Cycle 2

Moreover, a numerical improvement was seen in the majority of the productive parameters analysed in Cycle 2 compared to Cycle 1. The figures were significant in the case of the EPEF (European Production Efficiency Factor) and FCR (Feed Conversion Ratio) (Table 1).

Table 1. Comparison of production parameters between Cycle 1 and Cycle 2 *p-value < 0.005: statistically significant.

Additionally, in the second cycle the variable costs were reduced by R$ 0.12/kg (0.022 $/kg) live weight compared to the first cycle. Or in other words, in the second cycle with GUMBOHATCH®, the farms increased their profits by 22 R$ for each 1,000 kg of live weight produced.

Figure 2. Production cost differential between Cycle 1 and Cycle 2. R$ = Brazilian real

Conclusions

The results obtained in this study allow the conclusion to be drawn that vaccination with GUMBOHATCH® is safe and confers adequate protection against circulation of the variant IBDV in chickens under field conditions in Brazil. The differences observed in terms of efficacy between Cycle 1 and Cycle 2 appear to show that the vaccination programme based on the standard formulation immune complex vaccine was not providing adequate protection for the birds and field virus pressure had increased, with a negative impact on production results. The use of a new generation immune complex vaccine like GUMBOHATCH® allowed rapid colonization of the vaccine strain from one cycle to another, improving the immune status of the birds and production results.

Bibliography

1. Nakano et alt., 1972. Ocorrência da “Doença de Gumboro” no Brasil. Diagnóstico anátomo-patológico, Biológico (1972), 38:60-61. 2. Zachar et alt., 2016. Canadian Journal of Veterinary Research, Volume 80, Number 4, October 2016, pp. 255-261 3. Eterradossi and Saif, 2008. Infectious bursal disease. Diseases of Poultry. 12th ed. (2008), pp. 185–208. 4. Aline Padilha de Fraga et alt., Infection, Genetics and Evolution, Volume 73, September 2019, pp. 159-166 5. Ikuta et alt., 2001. Molecular characterization of Brazilian infectious bursal disease viruses. Avian Diseases (2001), pp. 297-306

La entrada Displacing IBDV variant strains with the use of a new generation immune complex vaccine se publicó primero en Gumboro Prevention.

Field experience in Brazil: comparison between a new generation and a standard formulated immune complex Gumboro vaccine

mireiadiaz — Mon, 05 Sep 2022 06:06:26 +0000

Immune complex Gumboro vaccines are formulated by mixing a well defined amount of an attenuated IBDV strain and a solution of specific antibodies against the same virus. But are all immune complex vaccines the same?GUMBOHATCH® is an immune complex vaccine with a new and unique formulation, in addition to introducing control parameters to ensure that all viral particles are completely coated with antibodies, that is, in the form of an immune complex. All these new improvements have resulted in a next generation immune complex vaccine, but, are there really benefits at the field level compared to other standard formulated immune complex vaccines?

Comparing GUMBOHATCH® with a standard formulated immune complex vaccine against Gumboro under field conditions in Brazil

A multicentre, positive-controlled and blind clinical trial was performed with the aim of evaluating the safety and efficacy of GUMBOHATCH^®, when administered via the in-ovo route under field conditions, compared with a standard formulated immune complex vaccine in Brazil. A total of 112,100 chicks were vaccinated in-ovo (18 days of incubation) with GUMBOHATCH® (n= 56,200) or with a standard formulated immune complex vaccine (n=55,900), following the manufacturer’s instructions. After hatching, the chicks were distributed to 3 commercial broiler farms located in the Paraná state. On each farm the two groups were housed in separate units under identical conditions and monitored up to the end of rearing (42 days of life). Several safety and efficacy parameters were evaluated during this period. No adverse reactions to either of the two vaccines were observed and similar hatchability and body weight after hatching were also observed in both groups. Although no Gumboro disease outbreak occurred on any of the farms, general productive parameters were slightly improved (numerically) in the case of houses vaccinated with GUMBOHATCH^® (Table 1).

Table 1. Productive results at the end of rearing (42 days of life). Statistically significant differences (p<0.05). *EPEF: European Production Efficiency Factor.

PCR results from bursal imprints evidenced replication of the vaccine virus from day 21 onwards in both groups, coinciding with a progressive decrease of the BB ratio (Figure 1).

Evolution of Bursa-to-body weight ratio (BB ratio) (mean+-SEM). *Statistically significant differences (p<0.005)

The development of antibody titres to the Gumboro virus after vaccination followed a similar pattern in both groups, with a progressive decrease in maternally-derived antibodies between days 0 and 21. However, in the case of the GUMBOHATCH® group, the maternally-derived antibodies were higher on each of the follow-up days (0, 14 and 21 days) compared with the standard formulated vaccine group. The decrease in the maternally-derived antibodies was followed by a rapid increase in vaccine-induced antibodies from day 28 onwards up to the end of rearing. Statistically significant differences (p<0.05) in vaccine-induced antibody titres were detected on day 35 in favour of the GUMBOHATCH® group (Figure 2), evidencing a faster humoral protection, even having always had higher levels of maternal antibodies.

Figure 2: Development of serum antibody titres to the IBD Virus; ELISA titre (mean± SEM) (cut-off value =357). *Statistically significant differences (p<0.05).

So, which are the main improvements we can observe with GUMBOHATCH® in the field under Brazil conditions?

The results obtained in this study allow the conclusion to be drawn that vaccination with GUMBOHATCH® is safe and confers a faster humoral protection against Gumboro disease for the whole productive cycle of broiler chicks when administered via the in ovo route under field conditions. The rapid humoral response observed with GUMBOHATCH®, compared to a standard formulated vaccine, even when higher maternal antibodies were present, may correspond to the new formulation and controls performed that prevent the neutralization of the vaccine virus when in contact with high levels of maternal antibodies. References:

Perozo et al. 2019. World Veterinarian Poultry Association Congress. 0262.

La entrada Field experience in Brazil: comparison between a new generation and a standard formulated immune complex Gumboro vaccine se publicó primero en Gumboro Prevention.

The 4 key points for efficacious IBDV hatchery vaccination

Adrià Martos — Fri, 04 Mar 2022 10:57:23 +0000

Hatchery vaccination is becoming more and more popular thanks to the many advantages it provides in terms of vaccination precision and performance. In the case of vaccination against IBDV, it also offers the possibility of vaccinating in the presence of maternally derived antibodies whilst providing the reliability of individual injection.

The benefits of hatchery IBDV vaccination are clear, however 4 crucial points need to be observed if these benefits are to really be achieved:

Biosecurity and vaccine storage

Daily biosecurity procedures are considered to be the best management practice to reduce the possibility of introducing and spreading infectious diseases to hatcheries.

Remember to follow external and internal biosecurity measures.
Choose the most suitable vaccine for the prevention of IBDV and follow the special precautions for transportation and storage in accordance with the manufacturer’s instructions:

Check the temperature and appearance of the lyophilizate at the time of receipt of the vaccine. > Ensure that the cold chain is not broken from the time the vaccine leaves the production facilities until it is applied. Discard a vaccine in which the cold chain has been broken. > A maximum and minimum thermometer should be kept in the fridge to verify that temperatures are always within the acceptable ranges.

Vaccine reconstitution

Vaccine management, temperature, time elapsed after reconstitution, etc. are parameters to be evaluated on the day of vaccination to ensure the best results.

Vaccines should be reconstituted in a clean room and operators should wash their hands before handling them.
Clean the end caps (vaccine vial, solvent bag) with a disinfectant wipe before inserting the needle.
Use single-use syringes and needles that are free of any disinfectants or chemical solutions.
Calculate the required volume of vaccine to be used, taking into account the dosage that will be administered to the birds.
Solvents require correct handling and use:

> Only the solvent specified by the manufacturer for the particular vaccine and presentation should be used. > Solvents may also be sensitive to heat or freezing, thus transportation and storage measures should also be followed. > Operators should be adequately trained to ensure that the solvent used is the correct one and that it is in good condition.

Reconstitution: follow the manufacturer’s instructions, using sterile equipment free from any residues of chemical disinfectants.
The vaccine should be inspected visually for any foreign particulate matter prior to administration. Reconstituted vaccines should be discarded after 1 hour of use. It is recommended that the bag should be labelled with the time of reconstitution.

Vaccine application

Correct quality management of the vaccines and correct application are crucial to ensure that the entire flock receives the correct dose.

Hatchery IBDV vaccines, in general, are intended to be administered to embryonated eggs of 18 days’ development or to 1-day-old chicks.
They usually allow successful early immunization of the chicks in the presence of MDA, and it is not necessary to calculate the appropriate time of vaccination.
Administer the vaccine according to the manufacturer’s recommendations for the chosen route of administration (in-ovo or subcutaneous injection).
Reconstituted solvent bags should be shaken every 15 min to avoid vaccine deposition during vaccination.

Vaccination audits and follow-up

Hatchery vaccination control audits should be carried out throughout the process to ascertain if there is room for improvement. In addition, the vaccination performance should also be analyzed to ensure that it was carried out correctly and that the animals are in good health and have a high productive performance.

The goal of IBDV vaccination follow-up is to monitor its effectiveness by evaluating different variables and critical control points:

Equipment and materials, environment, vaccine storage and vaccination process.
A dye should be mixed with the vaccine to allow visualization of the injection.
Serological response, molecular diagnosis by PCR, macroscopic evaluation of the bursa of Fabricius, vaccination performance and zootechnical parameters (body weight, FCR, mortality, EPEF, uniformity…).
The Global Hatchery Health Programme (GHHP) by HIPRA is a package of technical services focused on getting the most out of the incubation process by enhancing day-old chick health performance.

La entrada The 4 key points for efficacious IBDV hatchery vaccination se publicó primero en Gumboro Prevention.

GLOBAL HATCHERY HEALTH PROGRAMME – A service beyond vaccination for the prevention of Gumboro disease

Adrià Martos — Fri, 17 Dec 2021 08:48:28 +0000

Hatchery vaccination is increasing significantly and is becoming a very important practice for the poultry industry for the control of several economically important poultry viral diseases, such as Gumboro disease (IBD).

Immune complex and recombinant Gumboro vaccines can be applied at hatchery level, both in ovo and via the subcutaneous route, with the objective of giving a short window of time before the chicks are placed in potentially contaminated environments. In addition to early prevention, hatchery vaccination offers other important advantages such as the reliability of a full dose application, hygiene conditions, fewer vaccination errors, the fact that it is not dependent on water quality and that there is no need to calculate the optimal vaccination day. All these advantages should help to promote flock health, performance and a higher efficiency but principally when proper monitoring and control of all vaccine-related operations are implemented. To support poultry companies in ensuring this, HIPRA has developed a series of services included under the new GLOBAL HATCHERY HEALTH PROGRAMME (GHHP) that will bring innovation and real-time control of the HEALTH of the hatchery. GHHP consists of a range of distinctive services divided into three main blocks:

1. Optimization of vaccination procedures

GHHP offers services focused on guaranteeing correct vaccination procedures for all administration routes (in ovo or subcutaneous in the case of Gumboro), including innovative devices and the Smart Vaccination concept for vaccine verification through traceability.

Ensuring correct vaccination to reduce procedure failures and, consequently, to achieve better safety and efficacy of vaccination.

2. DOC quality control

Chick quality and vaccination quality are intrinsically linked, and one cannot be successful without the other. For this reason, GHHP is aimed at guaranteeing that the chicks leave the hatchery in the best condition thanks to DOC quality assessment through numerical and objective data:

Physical evaluation: based on the PAS REFORM “Pasgar Score” test, a formula that allows chick quality to be assessed with a numerical value.
Microbiological evaluation: the evaluation of the microbiological quality that works like a barometer of the processes associated with the breeders and the biosecurity of the hatchery.

This approach provides the possibility of anticipating challenges at field level.

3. KPI analysis

GHHP includes data science analysis (powered by HIPRASTATS®) to assess the key performance indicators at the hatchery level and to transform data into useful information to improve the decision-making process.

This service allows an in-depth analysis of the main variable factors that can affect final hatchability and 1st week mortality.

Through all these evaluations, critical points can be detected more easily, and this can help the hatchery team take better decisions. So, what benefits does this programme bring?

Unique real-time vaccination control through traceability.
Anticipation of field challenges.
Detection of areas of improvement through the hatchery’s data.
Savings in time and money by making the most of the vaccination process.

BIBLIOGRAPHY

Abdul-Cader, M. S. et al. (2018). Hatchery Vaccination Against Poultry Viral Diseases: Potential Mechanisms and Limitations. Viral Immunology, 31(1), 23–33.
Pas Reform – Hatchery Talks® Pasgar Score.

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Advantages of immune complex vaccines based on IgY of egg origin for the prevention of Infectious Bursal Disease

Advertis Agencia — Mon, 04 Oct 2021 10:47:00 +0000

Immune complex vaccines against Infectious bursal disease virus (IBDV) are formulated by mixing attenuated virus of a Infectious bursal disease and a solution of specific antibodies against the same virus (IgY) that will coat the vaccine virus. The complex formed (virus and antibodies) will protect the vaccine from its neutralization.

From the first immune complex vaccines developed in the 1990s until now, all of them have used specific IgY extracted from the serum of hyperimmunized animals as coating antibodies (Figure 1). Figure 1. Basis of the immune complex IBDV vaccines formulation. A newly formulated immune complex vaccine has now appeared on the market, GUMBOHATCH^®, which uses specific IgY extracted from eggs instead of IgY from serum.

But what are the main advantages behind this new formulation?

Discover them in the following video:

A new procedure for extracting the IgY from eggs has been developed in order to improve the consistency and capacity for production of the highest quality antibodies. The extraction of antibodies from egg yolks has many advantages compared to extraction from the serum. Since the antibodies are extracted from the yolks of laid eggs, the method of antibody production is non-invasive. Besides, through appropriate immunization strategies, the concentration of antibodies in the egg yolk can be maintained at optimal levels over time. This process, therefore, prevents the animals from bleeding and stress whilst it allows the harvest of large amounts of antibodies. The possibility of obtaining large quantities of IgY through extraction from eggs has changed the way of formulating immune complex vaccines, giving the possibility of adding high proportions of IgY to ensure a complete coating of all the virus particles.

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Avian immunosuppressive diseases: How does immunosuppression affect the poultry industry? – Dr. Miquel Nofrarias’ approach

Adrià Martos — Mon, 26 Jul 2021 07:04:08 +0000

Avian immunosuppressive diseases are often undetected and underestimated, but they have a significant direct and indirect economic impact by affecting flock performance, clinical disease, vaccine failures and increased use of antibiotics. Mishandling, stress, mycotoxins, and several pathogens, such as Infectious Bursal Disease virus, are the main causes of immunosuppression.

During the World Poultry Virtual Congress by HIPRA, Dr. Miquel Nofrarias explained the main causes and the impact of avian immunosuppressive disease on the poultry industry (see the recorded webinar below).

The role of the immune system is to fight against external agents and provide effective protection against infective microorganisms. There are two lines of defence, innate (or non-specific) immunity and adaptive (or specific) immunity.

Specific organs and cells are involved in the birds’ immune system, which are:

Primary lymphoid organs: composed of the bursa of Fabricius, the thymus and bone marrow.
Secondary lymphoid organs: composed of the spleen, circulating lymphocytes and several lymphoid cell aggregates along the gut, trachea, oesophagus, harderian gland, tonsils, etc.

What is immunosuppression?

It is a temporary or permanent state of depression of the immune system, meaning that there is a suboptimal immune response (innate, cellular or humoral immunity).

Immunosuppression is not a disease and it has no clinical signs, it is an expression or a consequence of something damaging or impairing the immune system.

How can we recognize immunosuppression?

There is no specific indicator that confirms it, but there are several factors that could point towards possible immunosuppression:

Atrophy of the lymphoid organs.
Increased mortality.
Less uniformity of the flock.
Poor performance: increased FCR, carcass condemnation…
Lower antibody titre after vaccination or vaccine failure.
Increased bacterial infection.

Main causes of immunosuppression

Management practices: such as suboptimal incubation conditions, temperature, ammonia, transport, etc., which stress the birds and deplete the immune response.
Mycotoxins: besides affecting the immune system, they also affect metabolic routes, reproduction, egg quality, intestinal function…
Infectious agents: Immunosuppression is usually the consequence of a depletion of B and T cells by pathogens.

Table 1 (IRTA CReSa). Infectious agents and the mechanism of action that leads to immunosuppression.

Impact of immunosuppression

Immunosuppressive viral diseases have an important economic impact due to direct but also to indirect losses.

Direct losses are related to specific mortality, which will depend on the virulence, age and breed of the birds and the presence or absence of passive immunity. In addition, immunosuppression has a high impact on flock performance, with impaired growth and condemnation of carcasses.

On the other hand, immunosuppression leads to secondary infections that will increase the use of antibiotics to control them, which is a major concern for human health.

Furthermore, the efficacy of vaccinations is reduced, causing indirect economic loss and increasing the risk of infection in unprotected animals.

Studies conducted by Mc Ilroy et al. (1989) documented the economic impact of broiler flocks with Infectious Bursal Disease subclinical infection compared to flocks without lesions, showing a 14% decrease in financial return, an 11% reduction in net income per 1000 birds and +0.8% increase in flock mortality.

In addition, McNulty et al. (1991) studied the impact of CAV seropositive broiler flocks at slaughter compared to CAV seronegative flocks, showing a 13% smaller net income per 1000 birds, a 2% worse feed conversion ratio and a 2.4% lower average weight.

Conclusions

Immunosuppression can result in significant direct and indirect economic losses.
It is caused by suboptimal environmental conditions, poor management practices, mycotoxins and several infectious diseases such as Infectious Bursal Disease.
The key to prevention of immunosuppression is to reduce stress, maintain appropriate management practices and follow strict vaccination programmes.

References:

McIlroy et al. (1989). Economic Effects of Subclinical Infectious Bursal Disease in Broiler Production. Avian Pathology 18(3): 465-80.
McNulty et al. (1991). Economic Effects of Subclinical Chicken Anemia Agent Infection in Broiler Chickens. Avian Diseases, 35(2), 263-268.
Immunosuppressive viral diseases in poultry

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Evolution of IBDV. What to expect in the coming years? Dr. Daral Jackwood’s approach

Adrià Martos — Tue, 13 Jul 2021 13:17:31 +0000

Infectious bursal disease (IBD) has been recognised as a significant problem in chickens since the 1960’s. Despite the use of vaccines to control IBDV, it continues to cause economic losses in the poultry industry. Antigenic drift in IBDV is thought to be responsible for the formation of antigenic variant strains of the virus that are successful in escaping the protection offered by vaccination programmes.

During the World Poultry Virtual Congress by HIPRA, Dr. Daral J. Jackwood exposed the antigenic drift of the IBDV and the evolution we should expect of the different strains of Gumboro disease in the coming years (see below the recorded webinar).

Infectious bursal disease is currently one of the most important contagious immunosuppressive diseases of poultry worldwide.

The irreversible immune suppression caused by IBDV in young chickens increases their susceptibility to a multitude of opportunistic avian pathogens that are normally non-pathogenic in healthy flocks. This results in a major economic impact on the broiler and layer chicken industries.

A study in Saskatchewan (Canada) estimates that the broiler industry there loses about 3.9 million kg of meat per year, a market value of over $14 million, from IBD infections (Zachar et al., 2016).

This figure could also increase as consumer demand for antibiotic-free chicken increases because many of the opportunistic bacterial infections that have occurred in immune suppressed chicken flocks were controlled by antibiotics.

IBDV prevention

IBDV control has only been possible through the use of efficacious vaccines, but vaccination efforts are complicated by the fact that frequent viral genetic mutations, reassortment of genome segments and recombination can potentially increase virulence and alter antigenicity, rendering vaccines and vaccine protocols less effective.

Moreover, eradication of the virus on infected farms is not practical, since the virus is highly contagious and very resistant to chemical and heat inactivation.

Antigenic Drift in the IBDV Birnavirus

The antigenic drift is defined as a kind of genetic variation in viruses, arising from the accumulation of mutations in the virus genes that code for virus-surface proteins that host antibodies recognise.

This results in a new strain of virus particles that is not effectively inhibited by the antibodies that prevented infection by previous strains. This makes it easier for the changed virus to spread throughout a partially immune population.

Antigenic drift in the IBDV Birnavirus has been attributed to substitution mutations in the hypervariable sequence region of the capsid protein VP2 (hvVP2; Figure 1) and it is thought to be the major event contributing to the alteration of the virus antigenicity.

Many molecular epidemiological studies have focused their research on the amino acids (in the hvVP2) that contribute most to the antigenic drift in the IBDV, which will affect the binding of neutralising antibodies produced by different IBDV strain vaccines (Jackwood and Somme-Wagner, 2011).

Differences in the antigenic drift between variant and vvIBDV field strains have also been observed (Michel and Jackwood, 2017).

FIGURE 1: Three-dimensional image of VP2 protein (A) located on the surface of the viral capsid of the IBDVs (B). Three VP2 molecules come together to form a trimer that makes up the virion surface. The loop structures on each VP2 project outward on the capsid. These loops are responsible for attachment and entry into the host cell. Antibodies directed to them will block attachment and entry of the virus into the B-cell and thus protect the chick from disease.

Research focused on changes occurring in the IBDV will be needed to control these evolving viruses. In addition, improved management in the vaccination programme of this economically devastating disease is and will be of critical importance to the global poultry industry.

References:

D.J. Jackwood and S.E. Sommer-Wagner. 2011. Amino acids contributing to antigenic drift in the infectious bursal disease Birnavirus (IBDV). Virology 409 (2011) 33–37.
L.O. Michel and D.J. Jackwood. 2017. Classification of infectious bursal disease virus into genogroups. Archives of Virology (2017) 162:3661–3670.

La entrada Evolution of IBDV. What to expect in the coming years? Dr. Daral Jackwood’s approach se publicó primero en Gumboro Prevention.

Improvements in Gumboro disease with immune complex vaccines

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GUMBOHATCH^® is a new immune complex vaccine against Gumboro disease developed by HIPRA. This new immune complex vaccine has introduced a different formulation (IgY of egg origin) and control parameters (free IgY detection and neutralization control) to ensure the complete coating of the IBDV virus. All these new improvements have resulted in a newly formulated immune-complex vaccine, which ensures the maintenance of the maximum potency of the vaccine and consistent results in the field, even in the presence of high levels of maternal antibodies¹.

Comparing GUMBOHATCH® with a standard formulated immune complex under field conditions in Europe

A multicentre, positive-controlled and blind clinical trial was performed with the aim of evaluating the safety and efficacy of GUMBOHATCH^®, when administered via the subcutaneous route under field conditions, compared with a standard formulated immune complex vaccine in Europe. A total of 160,731 one-day-old chicks were vaccinated via the subcutaneous route with GUMBOHATCH^® (n= 77,152) or with a standard formulated immune complex vaccine (n=83,579), following the manufacturer’s instructions. After vaccination, the chicks were distributed to 2 commercial broiler farms in France and to one farm in Belgium. On each farm the two groups were housed in separate units under identical conditions and monitored up to the end of rearing (35 days of life). Several safety and efficacy parameters were evaluated during this period. No adverse reactions to either of the two vaccines were observed and similar hatchability and body weight after hatching were also observed in both groups. Although no Gumboro disease outbreak occurred on any of the farms, general productive parameters were slightly improved (numerically) in the case of houses vaccinated with GUMBOHATCH^® (Table 1). Table 1. Productive results at the end of rearing (35 days of life). Statistically significant differences (p<0.05). *EPEF: European Production Efficiency Factor. PCR results from bursal imprints (Figure 1) and BB ratio evidenced that the replication of the vaccine virus started from day 21 onwards in both groups. Figure 1. PCR results from bursal imprints. Statistically significant differences (p<0.05). The evolution of antibody titres to the IBD virus after vaccination followed a similar pattern in both groups, with a progressive decrease in maternally-derived antibodies between days 0 and 21, followed by a rapid increase in vaccine-induced antibodies from day 28 onwards up to the end of rearing. However, statistically significant differences (p<0.05) in vaccine-induced antibody titres were detected on days 28 and 35 in favour of the GUMBOHATCH^® group, evidencing a faster induction of the humoral protection (Figure 2). Also, a numerical difference was observed in the percentage of serological positivity between groups, with a higher number of positive animals in the case of GUMBOHATCH^® at 28 and 35 days. Figure 2. Evolution of serum antibody titres to the IBD Virus; ELISA titre (mean± SEM) (cut-off value =357) (2.A) and evolution of serological positivity (2.B). *Statistically significant differences (p<0.05).

So, which are the main improvements we can observe with GUMBOHATCH^® in the field under Europe conditions?

The results obtained in this study allow the conclusion to be drawn that vaccination with GUMBOHATCH^® is safe and confers a faster humoral protection against Gumboro disease when compared with a standard-formulated immune complex vaccine. The more rapid humoral response observed with GUMBOHATCH^® compared to a standard formulated vaccine, may correspond to the new formulation and controls performed that prevent the neutralization of the vaccine virus when in contact with high levels of maternal antibodies. References:

Perozo et al. 2019. World Veterinarian Poultry Association Congress. 0262.

La entrada Improvements in Gumboro disease with immune complex vaccines se publicó primero en Gumboro Prevention.

Articles on Infectious Bursal Disease | Gumboro Prevention

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BIBLIOGRAPHY

Advantages of immune complex vaccines based on IgY of egg origin for the prevention of Infectious Bursal Disease

But what are the main advantages behind this new formulation?

Avian immunosuppressive diseases: How does immunosuppression affect the poultry industry? – Dr. Miquel Nofrarias’ approach

What is immunosuppression?

How can we recognize immunosuppression?

Main causes of immunosuppression

Impact of immunosuppression

Conclusions

Evolution of IBDV. What to expect in the coming years? Dr. Daral Jackwood’s approach

IBDV prevention

Antigenic Drift in the IBDV Birnavirus

Improvements in Gumboro disease with immune complex vaccines

Comparing GUMBOHATCH® with a standard formulated immune complex under field conditions in Europe

So, which are the main improvements we can observe with GUMBOHATCH® in the field under Europe conditions?

So, which are the main improvements we can observe with GUMBOHATCH^® in the field under Europe conditions?