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Infectious bursal disease (IBD), caused by the infectious bursal disease virus (IBDV), significantly threatens global poultry health by inducing immunosuppression and causing economic losses. To enhance vaccination efficacy, we engineered a transgenic strain of Eimeria acervulina (Ea-2C3d) expressing a fusion protein composed of IBDV VP2 and three tandem C3d segments (3C3d), utilizing C3d's adjuvant properties to boost immune responses. The transgene was generated by integrating codon-optimized VP2 and 3C3d sequences into the E. acervulina genome using restriction enzyme-mediated transfection. PCR, protein, and genome sequencing confirmed the successful integration and expression of VP2 fusion C3d, but only two copies of C3d were successfully expressed, due to a partial deletion of one C3d copy during the transfection process. In vivo studies demonstrated that Ea-2C3d elicited significantly higher anti-VP2 antibody titers than the parental Ea-VP2 strain (P < 0.05), especially following second immunization. Upon challenge with virulent IBDV, chickens immunized with Ea-2C3d displayed reduced bursal lesions (histopathological score ≤ 1) and maintained bursal integrity (bursal index >0.7), comparable to those receiving a commercial subunit vaccine. Despite reduced reproductive capacity in the transgenic parasites, Ea-2C3d maintained its immunogenicity and safety. These findings highlight that C3d adjuvant enhances VP2-mediated protection in a coccidial vector, presenting a novel dual-protection strategy against IBD and coccidiosis.

Infectious bursal disease virus (IBDV) is an acute and highly infectious RNA virus known for its immunosuppressive capabilities, chiefly inflicting rapid damage to the bursa of Fabricius (BF) of chickens. Current clinical control of IBDV infection relies on vaccination. However, the emergence of novel variant IBDV (nVarIBDV) has posed a threat to the poultry industry across the globe, underscoring the great demand for innovative and effective vaccines. Our previous studies have highlighted the critical role of IBDV VP5 as an apoptosis-inducer in host cells. In this study, we engineered IBDV mutants via a reverse genetic system to introduce amino acid mutations in VP5. We found that the mutant IBDV-VP5/3m strain caused reduced host cell mortality, and that strategic mutations in VP5 reduced IBDV replication early after infection, thereby delaying cell death. Furthermore, inoculation of chickens with IBDV-VP5/3m effectively reduced damage to BF and induced neutralizing antibody production comparable to that of parental IBDV WT strain. Importantly, vaccination with IBDV-VP5/3m protected chickens against challenges with nVarIBDV, an emerging IBDV variant strain in China, reducing nVarIBDV loads in BF while alleviating bursal atrophy and splenomegaly, suggesting that IBDV-VP5/3m might serve as a novel vaccine candidate that could be further developed as an effective vaccine for clinical control of IBD. This study provides a new clue to the development of novel and effective vaccines.

Functional M cells are differentiated by receptor activator of NF-κB ligand (RANKL) and capture of luminal antigens to initiate immune responses. We aimed to use postbiotic-based recombinant chicken RANKL (cRANKL) to promote M cell differentiation and test the efficacy of oral vaccines. Chicks were divided into three groups that were administered phosphate-buffered saline (PBS), cell extracts of wild-type Lactococcus lactis subsp. lactis IL1403 (WT_CE), or cell extracts of recombinant L. lactis expressing cRANKL (cRANKL_CE). The expression of the M cell marker was measured, and the gut microbiome was profiled. The efficiency of the infectious bursal disease (IBD) vaccine was tested after 12 consecutive days of administering cRANKL_CE. The chickens that were administered cRANKL_CE ( p  = 0.038) had significantly higher Annexin A5 ( ANXA5 ) mRNA expression levels than those in the PBS group (PBS vs. WT_CE, p  = 0.657). In the gut microbiome analysis, no significant changes were observed. However, the relative abundance of Escherichia-Shigella was negatively correlated ( r  =  − 0.43, p  = 0.019) with ANXA5 mRNA expression in Peyer’s patches. cRANKL_CE/IBD ( p  = 0.018) had significantly higher IBD-specific faecal IgA levels than PBS/IBD (PBS/IBD vs. WT_CE/IBD, p  = 0.217). Postbiotic-based recombinant cRANKL effectively improved the expression of M cell markers and the efficiency of oral vaccines. No significant changes were observed in the gut microbiome after administration of postbiotic-based recombinant cRANKL. This strategy can be used for the development of feed additives and adjuvants. Key points •  Postbiotic-based recombinant cRANKL enhanced the expression of ANXA5 in chicken. •  The relative abundance of Escherichia-Shigella was negatively correlated with ANXA5 expression. •  Postbiotic-based recombinant cRANKL effectively improved the efficiency of oral vaccine.

•Multivalent vHVT vaccines protect against HPAIVs, IBDV, and NDV challenges.•HVT COBRA H5 insert alone or in combination protects against diverse Gs/GD H5 HPAIV.•Vaccines against HPAIV provided clinical protection and reduced viral shedding. Vaccines are an essential tool for the control of viral infections in domestic animals. We generated recombinant vector herpesvirus of turkeys (vHVT) vaccines expressing computationally optimized broadly reactive antigen (COBRA) H5 of avian influenza virus (AIV) alone (vHVT-AI) or in combination with virus protein 2 (VP2) of infectious bursal disease virus (IBDV) (vHVT-IBD-AI) or fusion (F) protein of Newcastle disease virus (NDV) (vHVT-ND-AI). In vaccinated chickens, all three vHVT vaccines provided 90–100% clinical protection against three divergent clades of high pathogenicity avian influenza viruses (HPAIVs), and significantly decreased number of birds and oral viral shedding titers at 2 days post-challenge compared to shams. Four weeks after vaccination, most vaccinated birds had H5 hemagglutination inhibition antibody titers, which significantly increased post-challenge. The vHVT-IBD-AI and vHVT-ND-AI vaccines provided 100% clinical protection against IBDVs and NDV, respectively. Our findings demonstrate that multivalent HVT vector vaccines were efficacious for simultaneous control of HPAIV and other viral infections.

Infectious bursal disease virus (IBDV) causes an acute, highly contagious and immunosuppressive disease in 3–5‐week‐old chicken, called infectious bursal disease (IBD). Current vaccines targeting the hypervariable VP2 gene fail to provide cross‐protection against different IBDV strains, necessitating the development of novel diagnostic and preventive strategies that explore other candidate genes to ensure immune efficacy. Here, VP3, a conserved nucleocapsid protein of IBDV, was selected for further analysis. A prokaryotic expression vector, pET‐32a‐IBDV‐VP3, was constructed, followed by expression and purification of the recombinant protein. Following the intraperitoneal injection of recombinant proteins into the mice, eight monoclonal antibodies (mAbs) were identified by hybridoma cell fusion, clone purification, and immunological assays. Among the mAbs, mAb 19D8 effectively neutralized IBDV infection during viral attachment and penetration. Antigenic epitopes of mAb 19D8 were identified using alanine‐scanning mutagenesis. Our results showed that four amino acids, F20, K21, T23, and E25, located on an α‐helix of the VP3, were the key amino acids recognized by 19D8. Homologous and structural analyses revealed that these sites were highly conserved across different IBDV strains from diverse regions. These findings provide crucial insights into the antigenicity of VP3 and underscore the potential of VP3 as a target for the development of broad‐spectrum diagnostic tools and cross‐protection vaccines against IBDV.

•Effect of IBD vaccine (228E®) on S. Enteritidis infected chickens was indicated.•The recorded mortalities were higher in the 228E®+SE infected group.•The anti-S. Enteritidis antibody titres were higher in the SE infected group.•The 228E®+SE group had higher bursal lesion scores than the SE infected group.•Chickens given IBDV vaccine failed antibody response to the S. Enteritidis. Chickens infected with both infectious bursal disease virus (IBDV) and Salmonella had higher mortality. In this work, we investigated the effect of IBDV vaccine (modified live-virus bursal disease vaccine, Nobilis strain 228E®) on experimentally infected chickens with Salmonella Enteritidis (SE). Four experimental groups were included in this study, negative control group, 228E®group, 228E®+SE infected group, and SE infected group. Chickens were ocularly administrated 228E® at 12days of age and orally infected with S. Enteritidis at 13days of age. Sera, intestinal fluid, blood, cloacal swabs and tissue samples were collected at 1, 2 and 3weeks post vaccination (PV). The recorded mortalities were higher in the 228E®+SE infected group, compared to the SE infected group. The anti-S. Enteritidis serum antibody titer and the intestinal mucosal IgA level were higher in the SE infected group at 2 and 3weeks PV, compared to 228E®+SE infected group. S. Enteritidis fecal shedding and organ colonization were significantly higher in the 228E®+SE infected group than the SE infected group at 2 and 3weeks PV. The 228E®+SE group had significantly lower bursa to body weight ratios at 2 and 3weeks PV, as well as had higher bursal lesion scores than the SE infected group. IBDV vaccine depressed the specific-SE systemic and mucosal antibody responses, but did not affect the specific-SE cellular immune responses. Chickens administrated IBDV vaccine, followed by S. Enteritidis infection, could cause a significant effect on the bursa of Fabricius, resulting in failure of systemic and mucosal antibody responses to the S. Enteritidis and reduce the elimination and the clearance of S. Enteritidis.

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.

Background Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), is a highly contagious disease that is prevalent worldwide and poses a significant threat to the poultry industry. While commercially available vaccines are used for prevention, IBD outbreaks remain frequent. Objective The continuous mutation of virulent strains and their ability to evade traditional vaccine protection complicate IBD control, which necessitates the development of novel vaccines and a deeper understanding of viral mutation mechanisms. Method Utilizing the self-assembly capability of ferritin (Fe), the hypervariable region (HVR) protein of a novel variant IBDV (NvIBDV) VP2 was displayed on the ferritin shell, forming regular nanoparticles. The full-length NvIBDV VP2 protein and the NvIBDV VP2-HVR-Fe fusion protein were prokaryotically expressed in E. coli and purified to prepare a VP2 protein vaccine and a VP2-Fe nanoparticle vaccine. An inactivated NvIBDV vaccine served as a control for evaluating immunogenicity and protection. Results Recombinant prokaryotic expression vectors pET-VP2-Fe (encoding VP2-HVR-Fe) and pET-VP2 (encoding full-length VP2) were successfully constructed. Soluble VP2-Fe and VP2 proteins were expressed and purified. Electron microscopy confirmed the formation of a cage-like nanoparticle structure for VP2-Fe. Immunization of SPF chickens with NvIBDV VP2-Fe nanoparticles induced a robust immune response characterized by high antibody titers and a significantly high protection rate against viral challenge. Conclusion The successfully constructed recombinant subunit nanoparticle vaccine, which displays the NvIBDV VP2 HVR on ferritin, effectively increased the antibody titer and provided superior immune protection. This approach offers a feasible strategy for developing novel IBDV subunit vaccines.

•This study constructed a bivalent chimeric virus-like particle vaccine (ND-IBD cVLPs) displaying the ND virus (NDV) HN protein and the IBD virus (IBDV) VP2 protein.•ND-IBD cVLPs stimulated highly effective HI antibody levels against NDV HN protein and ELISA antibody levels against the IBDV VP2 protein.•ND-IBD cVLPs provided complete protection against virulent NDV and IBDV challenges and alleviated the pathological damage caused by viral infection. Newcastle disease (ND) and infectious bursal disease (IBD) pose significant threats to the chicken industry, causing substantial economic losses. Currently, immunization through vaccination is the most effective strategy to prevent ND and IBD but currently used traditional vaccines, including inactivated or attenuated vaccines, face challenges in achieving a balance between immunogenicity and safety. To develop a green and efficient novel vaccine for ND and IBD, we developed a bivalent chimeric virus-like particle vaccine (ND-IBD cVLPs) displaying the ND virus (NDV) HN protein and the IBD virus (IBDV) VP2 protein based on the ND VLPs carrier platform and insect baculovirus expression system. This study aimed to evaluate the immunogenicity and protective efficacy of ND-IBD cVLPs in specific pathogen-free chickens. Chickens were immunized with 50 µg of purified ND-IBD cVLPs at 7 days old, boosted at 21 days old, and challenged at 42 days old. The results demonstrated that ND-IBD cVLPs stimulated highly effective hemagglutination inhibition antibody levels against NDV HN protein and enzyme-linked immunosorbent assay antibody levels against the IBDV VP2 protein. Furthermore, ND-IBD cVLPs provided complete protection against virulent NDV and IBDV challenges and mitigated pathological damage to the lung caused by NDV infection and the bursa of Fabricius caused by IBDV infection. These findings suggest that ND-IBD cVLPs hold promise as a safe and efficient novel vaccine candidate for the effective prevention of ND and IBD, extending the development of a foreign protein delivery platform of ND VLPs.

•Modified live (MdLV) rather than HVT-IBDV vaccine delays neonatal varIBDV infection.•varIBDV replicates early in HVT-IBDV compared to MdLV vaccinated chicks.•HVT-IBDV vaccine induces suppression of T-cell response.•First week after HVT-IBDV vaccination demands strict biosecurity. Chickens are commonly processed around 35–45days of age in broiler chicken industry hence; diseases that occur at a young age are of paramount economic importance. Early age infection with infectious bursal disease virus (IBDV) results in long-lasting immunosuppression and profound economic losses. To our knowledge, this is the first study comparing the protection efficacy of modified live (MdLV) IBDV and herpesvirus turkey (HVT)-IBDV vaccines against early age variant IBDV (varIBDV) infection in chicks. Experiments were carried out in IBDV maternal antibody (MtAb) positive chicks (n=330), divided into 6 groups (n=50–60/group), namely Group 1 (saline), Group 2 (saline+varIBDV), Group 3 (HVT-IBDV), Group 4 (HVT-IBDV+varIBDV), Group 5 (MdLV) and Group 6 (MdLV+varIBDV). HVT-IBDV vaccination was given via the in ovo route to 18-day-old embryonated eggs. MdLV was administered via the subcutaneous route in day-old broilers. Group 2, Group 4 and Group 6 were orally challenged with varIBDV (SK-09, 3×103 EID50) at day 6 post-hatch. IBDV seroconversion, bursal weight to body weight ratio (BBW) and bursal histopathology were assessed at 19 and 35days of age. Histopathological examination at day 19 revealed that varIBDV-SK09 challenge caused severe bursal atrophy and lower BBW in HVT-IBDV but not in MdLV vaccinated chicks. However by day 35, all challenged groups showed bursal atrophy and seroconversion. Interestingly, RT-qPCR analysis after varIBDV-SK09 challenge demonstrated an early (9days of age) and significantly high viral load (∼5744 folds) in HVT-IBDV vaccinated group vs unvaccinated challenged group (∼2.25 folds). Furthermore, flow cytometry analysis revealed inhibition of cytotoxic CD8+ T-cell response (CD44-downregulation) and decreased splenic lymphocytes counts in chicks after HVT-IBDV vaccination. Overall, our data suggest that MdLV delays varIBDV pathogenesis, whereas, HVT-IBDV vaccine is potentially immunosuppressive, which may increase the risk of early age varIBDV infection in broilers.