Control Of Infectious Bursal Disease Research Articles

Construction and Evaluation of the Immunogenicity and Protective Efficacy of Recombinant Replication-Deficient Human Adenovirus-5 Expressing Genotype VII Newcastle Disease Virus F Protein and Infectious Bursal Disease Virus VP2 Protein.

Newcastle disease (ND) and infectious bursal disease (IBD) are two key infectious diseases that significantly threaten the health of the poultry industry. Although existing vaccinations can effectively prevent and treat these two diseases through multiple immunizations, frequent immunization stresses significantly impact chicken growth. In this study, three recombinant adenoviruses, rAd5-F expressing the NDV (genotype VII) F protein, rAd5-VP2 expressing the IBDV VP2 protein, and rAd5-VP2-F2A-F co-expressing F and VP2 proteins, were constructed using the AdEasy system. The F and VP2 genes of the recombinant adenoviruses could be transcribed and expressed normally in HEK293A cells as verified by RT-PCR and Western blot. The three recombinant viruses were shown to have similar growth kinetics as rAd5-EGFP. Compared with the PBS and rAd5-EGFP groups, SPF chickens immunized with recombinant adenoviruses produced higher antibody levels, more significant lymphocyte proliferation, and significantly higher CD4+/CD3+ and CD8+/CD3+ cells in peripheral blood. The survival rate of SPF chickens immunized with rAd5-F and rAd5-VP2-F2A-F after the challenge with DHN3 was 100%, and 86% of SPF chickens showed no viral shedding at 7 dpc. The survival rate of SPF chickens immunized with rAd5-VP2 and rAd5-VP2-F2A-F after the challenge with BC6/85 was 86%. rAd5-VP2 and rAd5-VP2-F2A-F significantly inhibited bursal atrophy and pathological changes compared to the rAd5-EGFP and PBS groups. This study provides evidence that these recombinant adenoviruses have the potential to be developed into safe and effective vaccine candidates for the prevention and control of ND and IBD.

Genetic Insight into the Interaction of IBDV with Host-A Clue to the Development of Novel IBDV Vaccines.

Infectious bursal disease virus (IBDV) is an immunosuppressive pathogen causing enormous economic losses to the poultry industry across the globe. As a double-stranded RNA virus, IBDV undergoes genetic mutation or recombination in replication during circulation among flocks, leading to the generation and spread of variant or recombinant strains. In particular, the recent emergence of variant IBDV causes severe immunosuppression in chickens, affecting the efficacy of other vaccines. It seems that the genetic mutation of IBDV during the battle against host response is an effective strategy to help itself to survive. Therefore, a comprehensive understanding of the viral genome diversity will definitely help to develop effective measures for prevention and control of infectious bursal disease (IBD). In recent years, considerable progress has been made in understanding the relation of genetic mutation and genomic recombination of IBDV to its pathogenesis using the reverse genetic technique. Therefore, this review focuses on our current genetic insight into the IBDV's genetic typing and viral genomic variation.

Modelling Infectiology of Bursal Disease in Chicks with Control Measures

This paper focuses on mathematical control of infectious bursal disease in chicks. The model boundedness and the control measures to reduce the spreads of the disease have well analytically examined. The theory of Pontryagin’s maximum principle used in analysing necessary conditions to combat the disease. Numerically, forward backward sweep method and fourth-order Runge-Kutta scheme using the forward solution of the state equations was applied. The outcome indicates that the combination of vaccination of chicks and environmental sanitation as the most cost-effectiveness strategy to combat the spread of IBD with limited resources. Therefore, IBD can be controlled if the poultry farmers will effectively apply vaccination of chicks and environmental sanitation.

Six decades of infectious bursal disease in poultry: The journey so far and challenges ahead


 
 
 Despite six decades of concerted efforts, Infectious bursal disease (IBD) still remains a major threat to the poultry industry worldwide. Most importantly, the emergence of variant and very virulent strains of infectious bursal disease virus (IBDV) has dramatically changed the epidemiology of the disease, thus resulting in the renewed efforts in the search for effective control measures. Currently, live attenuated, inactivated, and immune-complex vaccines are among the immune-therapeutic approaches employed for the control of IBD in the field alongside adequate biosecurity, albeit with various degrees of success and limitations. Progress in genetic engineering has allowed the generation of reverse genetic IBDV mutants, recombinant live viral vectors expressing the IBDV VP2 immunodominant protein, intra-serotypic recombinant IBDV viral-like particle co-expressing the outer capsid protein structures derived from 2 or more serotype 1 strains or the incorporation of either VP2 or VP2-4-3 polyprotein sequences alongside molecular adjuvants that can be used as IBD vaccine candidates to elicit an immune response. However, despite these advances, outbreaks are still reported even in flocks that have up to date vaccination records and somewhat excellent management practices. This paper reviews aspect of genetic characteristics of IBDV and reflects on the progress and future challenges in providing effective IBD vaccine to achieve effective control of both classical and very-virulent IBDV serotypes that constitute a major devastation to poultry production and health.
 
 

Characterization and pathogenicity of a naturally reassortant and recombinant infectious bursal disease virus in China.

Infectious bursal disease virus (IBDV), an Avibirnavirus, is the pathogen of infectious bursal disease, which is a severely immunosuppressive disease in 3-15-week-old chickens. Different phenotypes of IBDV, including classical, variant, very virulent (vv) and attenuated IBDV, have been reported in many chicken-rearing countries worldwide. Here, we isolated and identified a naturally reassortant and recombinant IBDV (designated GXB02) from 20-day-old chickens with clinicopathological changes of infectious bursal disease (IBD) in Guangxi Province, China. Whole genomic sequencing showed that the strain GXB02 simultaneously has both reassortant and recombinant characteristics with segments A and B being derived from recombinant intermediate vaccine strain and classic strains of IBDV. Segment A of strain GXB02 was incorporated into the skeleton of an intermediate IBDV vaccine strain (W2512), where the breakpoints of two recombinant events located at nucleotide positions 1468 and 1648 were replaced by reassortant vvIBDV (PK2) and vvIBDV (D6948) of segment A, respectively. We used this GXB02 strain to inoculate 21-day-old specific-pathogen-free chickens to evaluate its pathogenicity. Strain GXB02 has clinicopathologic characteristics of IBD with severe bursal lesions, as evidenced by necrosis, depletion of lymphocytes, and follicle atrophy, indicating that reassortment with classical strains in segment B or/and recombination with very virulent strains increased pathogenicity of the strain GXB02 in chickens. These findings provide important insights into the genetic exchange between classic and attenuated strains of IBDV with two recombinant events occurring at the intermediate derivative segment A with vvIBDV strains, thereby increasing the difficulty of prevention and control of IBD due to novel reassortant-recombinant strains.

Identification and Pathogenicity Evaluation of a Novel Reassortant Infectious Bursal Disease Virus (Genotype A2dB3).

Infectious bursal disease virus (IBDV) is a non-enveloped, bi-segmented double-stranded RNA virus and the causative agent of a poultry immunosuppressive disease known as infectious bursal disease (IBD). The novel variant IBDV (nVarIBDV) recently posed a great threat to the development of the poultry industry. In this study, we identified a novel segment-reassortant IBDV strain, IBDV-JS19-14701 (Genotype A2dB3). Phylogenic analysis showed that Segments A and B of IBDV-JS19-14701 were derived from emerging nVarIBDV (Genotype A2dB1) and long-prevalent HLJ0504-like strains (Genotype A3B3) in China, respectively. The pathogenicity of IBDV-JS19-14701 was further evaluated via animal experiments. IBDV-JS19-14701 exhibited a similar virulence to chickens with the nVarIBDV. The identification of this reassortment event is beneficial for understanding the epidemiology of nVarIBDV and will contribute to the efficient prevention and control of IBD.

Safety and Efficacy Profile of Live, Intermediate Plus Vaccine Against Infectious Bursal Disease Based on Strain G6.

Infectious bursal disease (IBD) is an acute, highly contagious, immunosuppressive disease of young chickens that causes considerable economic loss in the poultry industry worldwide. Vaccination with live attenuated vaccines is still the most important method used for the control and prevention of IBD in chickens. Here we present the results of in vitro characterization, as well as efficacy and safety testing of a live, intermediate plus vaccine against IBD based on strain G6. Strain characterization confirmed that G6 strain is an intermediate plus strain, showing a high degree of homology with the existing vaccine strains of the same virulence. Safety studies showed that chickens can be vaccinated from 10 days of age. Onset and duration of immunity in specific pathogen free and maternally derived antibodies (MDA) chickens was proven to be 14 and 35 days after vaccination, respectively. When immunizing MDA-positive chickens, vaccine is capable of breakthrough at a titer of ≤500 ELISA units. The field trial conducted on commercial broilers showed a 95% protection against vvIBDV challenge. Stability of the freeze-dried vaccine after reconstitution was confirmed over a period of 3 h. Overall, IBD G6 vaccine has shown good safety and efficacy profile in accordance with European Pharmacopoeia requirements.

The Full Region of N-Terminal in Polymerase of IBDV Plays an Important Role in Viral Replication and Pathogenicity: Either Partial Region or Single Amino Acid V4I Substitution Does Not Completely Lead to the Virus Attenuation to Three-Yellow Chickens.

Infectious Bursal Disease Virus (IBDV) has haunted the poultry industry with severe, prolonged immunosuppression of chickens when infected at an early age and can easily lead to other secondary infections. Understanding the pathogenic mechanisms could lead to effective prevention and control of Infectious Bursal Disease (IBD). Evidence suggests that the N-terminal domain of polymerase in segment B plays an important role, but it is not clear which part or residual is crucial for the pathogenicity. Using a reverse genetics technique, a molecular clone (rNN1172) of the parental vvIBDV strain NN1172 was generated, and its pathogenicity was found to be the same as the parental virus. Then, three recombinant chimeric viruses were rescued based on the rNN1172 and substituted with the counterparts in the N-terminal domain of the attenuated vaccine strain B87: the rNN1172-B87VP1a (substituting the full region of the 1–167 aa residuals), the rNN1172-B87VP1a∆4 (substituting the region of the 5–167 aa residuals), and the rNN1172-VP1∆4 (one single aa residual substitution V4I), to better explore the role of the N-terminal domain of polymerase on the viral pathogenicity. Interestingly, all these substitutions played different roles in the viral pathogenicity: the mortality of the rNN1172-B87VP1a-challenged chickens was significantly reduced from 30% to 0%. No obvious lesion was found in the histopathological examination, and the lowest viral genome copy number was also detected in the bursa when compared to the parental and two other recombinant viruses. The mortalities caused by rNN1172-B87VP1a∆4 and rNN1172-B87VP1∆4, respectively, were all reduced to 10% and had a delayed onset of death. Our results also revealed that the pathogenicity of the IBDV was consistent with the viral replication efficiency in vivo (bursae). This study demonstrated that the full region of the N-terminal of polymerase plays an important role in viral replication and pathogenicity, but the substitutions of its partial region or a single residual do not completely lead to the virus attenuation to Three-Yellow chickens, although that significantly reduces its pathogenicity.

A reassortment vaccine candidate of the novel variant infectious bursal disease virus

Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), is the most important immunosuppressive disease threatening the poultry industry worldwide. Recently, the novel variant IBDV has been emerging in large-scale in Asia including China and is becoming a new threat to the healthy development of the poultry industry, but no ideal vaccine is available. Therefore, it is necessary and urgent to develop a new vaccine against the novel variant IBDV. In this study, based on the skeleton of an attenuated vaccine strain Gt, a reassortment virus strain rGtVarVP2 was constructed for the first time, which could express the main protective antigen VP2 of the novel variant IBDV and replicate well in cell culture. Subsequently, the safety and effectiveness of rGtVarVP2 were further evaluated using animal experiments. The rGtVarVP2 is nonpathogenic to specific-pathogen-free (SPF) chicken. The immunization of rGtVarVP2 could induce the specific neutralizing antibodies against the novel variant IBDV. The challenge protection tests further confirmed the effectiveness of the IBDV reassortment virus rGtVarVP2. No atrophy and obvious lesions were observed in the immunization group while the bursae of non-immunization control group were severely destroyed after challenge, which showed that rGtVarVP2 could provide complete protection against the novel variant IBDV. These data indicate that the vaccine candidate (rGtVarVP2 strain) is safe and effective, which is of great significance for comprehensive control of IBD and healthy breeding.

Advances in vaccine research against economically important viral diseases of food animals: Infectious bursal disease virus

Numerous reviews have been published on infectious bursal disease (IBD) and infectious bursal disease virus (IBDV). Many high quality vaccines are commercially available for the control of IBD that, when used correctly, provide solid protection against infection and disease caused by IBDV. Viruses are not static however; they continue to evolve and vaccines need to keep pace with them. The evolution of IBDV has resulted in very virulent strains and new antigenic types of the virus. This review will discuss some of the limitations associated with existing vaccines, potential solutions to these problems and advances in new vaccines for the control of IBD.

The Characteristics of an Ovine Lymphoid Cell-Line sensitive to Vaccinal Infectious Bursal Disease Virus Strain.

Infectious bursal disease (IBD), also known as Gumboro disease, is a globally well-known disease with a significant socio-economic effect. For control of IBD, several commercial egg- and cell-based vaccines are prepared. The cell-based IBD vaccines are significantly cost-effective; however, it is essential to confirm their safety and efficacy. The main cell line used to product the cell-based IBD vaccines, is a primary chicken embryo fibroblast (CEF). Nevertheless, manipulation of CEF is extremely challenging and time-consuming. This study aimed to characterize a sensitive suspension cell culture from ovine lymphoid, according to WHO technical report series; No. 978, Annex III. This authentication covered the growth curves, sensitivity, stability, karyotyping and identifying the adventitious agents. This cell line passed all defined tests and was considered as a suitable one for IBD vaccine preparation in a large scale.

An immunoinformatic assay to design bio adjuvanted vaccine against infectious bursal disease virus

Infectious bursal disease virus (IBDV) causes highly contagious and immunosuppressive disease in young chickens worldwide. The control of infectious bursal disease (IBD) depends mainly on vaccination and strict hygiene management of poultry farms, but the disease continues to pose an important threat to the commercial poultry industry. Recently, secondgeneration vaccines based on expression of VP2 in various vectors have been developed as new strategies for vaccination against IBD. A series of the vaccines were made using different adjuvant to examine their immunogenicity. In this study we explore the idea of using TLR7 as bio adjuvant to stimulate immune responses against IBDV. Eight conserved TLR7 motifs were found among Homo sapiens, Mus musculus, and Gallus gallus following alignment of the related sequences. Each of the TLR7 motif was fused to VP2 fragment and VP2/TLR7-1 to -8 constructs were designed. By using in silico analysis include physicochemical properties determination, protein structures prediction, antigenic site determination, and evaluation of model quality, one of the chimeric proteins was subjected to introduce as vaccine candidate. The results indicate that some TLR7 motifs can be potentially used as bio adjuvant for induction of immune responses against IBDV. It is necessary to determine the potential role of the peptide in induction of immunity against IBDV infection in chicken.

Characterization of field and vaccine infectious bursal disease viruses from Nigeria revealing possible virulence and regional markers in the VP2 minor hydrophilic peaks

Outbreaks of infectious bursal disease in vaccinated chicken flocks are frequent in Nigeria. For the control of infectious bursal disease, live vaccines based on foreign infectious bursal disease virus (IBDV) strains are used. The present study investigated the phylogenetic relationship between field and vaccine IBDV strains from northwestern Nigeria. Thirty field IBDV strains and three commercial vaccines strains were characterized through sequencing the VP2 hypervariable region. In addition, the complete genome segment A coding region for two vaccines and two field strains was sequenced. The deduced amino acid sequences (position 212 to 331) of IBDV strains from Nigeria and other regions of the world were aligned and possible regional and virulence markers were identified associated with VP2 minor hydrophilic peaks. Reversion to virulence of a vaccine strain with a Q to L mutation at position 253 was observed. Phylogenetic analyses revealed a unique cluster of northwest Nigerian field IBDV strains alone or related to imported characterized classical and very virulent IBDV vaccines. The results suggest that when IBDV strains spread from their region of origin to a different region they mutate alongside indigenous field strains but may retain their identity on the VP2 region.

Evaluation of live gumboro vaccine prepared from local variant strain for control of infectious bursal disease in Egypt

Aim: The present study was designed to evaluate live Gumboro (IBD) vaccine prepared from local variant isolated strain (Egy-IBD Var 2009 Vp2 gene-, partial cds submitted in gen bank at accession no. : JN 118617) for controlling IBD problem in Egypt. Material and Methods: Local isolated variant strain was adapted on Baby Grivet Monkey kidney cell line -70(BGM-70) 7.5 4.5 used for preparation of tissue culture (T.C) live vaccine. T.C IBDV had a titer of 10 TCID /ml (10 TCID per dose) after 50 50 five passages in BGM-70 cell culture. Evaluation of prepared vaccine was done in vitro by measuring ELISA, and in vivo by protection % against very virulent or variant field IBD isolated strains. Result: Evaluation revealed that the prepared vaccine was safe; sterile; pure; non-immunosuppressive; and efficient. The Geometric Mean Titer (GMT) of ELISA for the prepared vaccine was 8271 and more than 10000 in compared with different commercial IBD vaccines; while protection percentage gave 96-100%; 92-96% and 96-98% in groups vaccinated with commercial (intermediate; intermediate plus and classical) IBD vaccines; respectively in compared to 96-100% in group vaccinated with local prepared vaccine when challenged with very virulent or variant IBD isolated strains. Conclusion: We can use live T.C. IBD vaccine prepared from local variant isolated virus strain as method for control IBD disease in Egypt.

Immune Complex Vaccines for Chicken Infectious Anemia Virus

Infection of maternal, antibody-negative chickens with chicken infectious anemia virus (CIAV) can cause clinical disease, while infection after maternal antibodies wane often results in subclinical infection and immunosuppression. Currently, vaccines are not available for vaccination in ovo or in newly hatched chickens. Development of CIAV vaccines for in ovo use depends on the ability to generate vaccines that do not cause lesions in newly hatched chicks and that can induce an immune response regardless of maternal immunity. Immune complex (IC) vaccines have been successfully used for control of infectious bursal disease, and we used a similar approach to determine if an IC vaccine is feasible for CIAV. Immune complexes were prepared that consisted of 0.1 ml containing 10(5.4) tissue culture infective dose 50% of CIA-1 and 0.1 ml containing 10 to 160 neutralizing units (IC Positive [ICP]10 to ICP160), in which one neutralizing unit is the reciprocal of the serum dilution required to protect 50% of CU147 cells from the cytopathic effects caused by CIA-1. Virus replication was delayed comparing ICP80 and ICP160 with combinations using negative serum (IC Negative [ICN]80 or ICN160). In addition, the number of birds with hematocrit values <28% were decreased with ICP80 or ICP160 compared to ICN80 or ICN160. Seroconversion was delayed in ICP80 and ICP160 groups. To determine if ICP80 or ICN 160 protected against challenge, we vaccinated maternal, antibody-free birds at 1 day of age and challenged at 2 wk or 3 wk of age with the 01-4201 strain. Both ICP80 and ICP160 protected against replication of the challenge virus, which was measured using differential quantitative PCR with primers distinguishing between the two isolates. Thus, in principle, immune complex vaccines may offer a method to protect newly hatched chicks against challenge with field virus. However, additional studies using maternal, antibody-positive chicks in combination with in ovo vaccination will be needed to determine if immune complex vaccines will be useful to protect commercial chickens.

Biochemistry and Immunology of Infectious Bursal Disease Virus

Introduction. The aetiological agent of infectious bursal disease (IBD), IBD virus (IBDV), belongs to a new group of viruses referred to as ‘birnaviruses’ (Dobos et al., 1979), which has been characterized only recently (Brown, 1986). There are excellent reviews dealing with the clinical, pathological, serological and epidemiological aspects of IBDV infection (Faragher, 1972; Becht, 1980; Okoye, 1984; Cummings et al., 1986). The molecular biology of birnaviruses has also been reviewed (Dobos &amp; Roberts, 1983) but with an emphasis on infectious pancreatic necrosis virus (IPNV), the birnavirus genus prototype. The purpose of the present review is to compile information on structural and immunological aspects of IBDV. These are subjects of much recent interest, and have great relevance to the control of IBD in chickens. IBD is a highly contagious viral disease of young chickens which is characterized by destruction of the lymphoid cells in the bursa of Fabricius; other lymphoid organs are also affected but to a lesser degree (Cheville, 1967).

Immunization of Chickens for the Control of Infectious Bursal Disease

Six experiments were conducted involving 790 chickens inoculated with IBD (infectious bursal disease) vaccine produced at this station to determine a suitable age and route of vaccination. Vaccinated birds resisted a challenge dose that caused 10–20% mortality among unvaccinated challenged controls; whereas, there were no deaths among vaccinates.A total of 3,092,864 chicks in 135 flocks on 88 farms in Alabama and Mississippi were vaccinated at an average age of 5 days via the drinking water or intraocularly in initial trials. Mortality following vaccination averaged <0.78% during the reaction period (5 to 7 days) compared with an average 5% mortality in natural outbreaks on the same farms. There were no relapses or natural outbreaks in any of the 135 vaccinated flocks.