Immunization with recombinant Erns-LTB fusion protein elicits protective immune responses against bovine viral diarrhea virus

Wang, Shenghua; Yang, Guanghui; Nie, Jiawei; Wang, Jing; Wang, Yixuan; Du, Mengze; Guo, Liang; Yang, Ren-Jie; Zhu, Yaohong

doi:10.1016/j.vetmic.2021.109084

Cited by 7 publications

(3 citation statements)

References 31 publications

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“…The immunogenicity data from mice studies revealed that LTB-PRRSV is capable of inducing strong systemic IgG response without adjuvants, which is in agreement with the adjuvant effects extensively reported for epitopes fused to LTB [38,39]. However, the tested adjuvants improved the quality and robustness of the induced immune response in the short term as revealed by the IgG levels measured two weeks after the last boosting.…”

Section: Discussionsupporting

confidence: 85%

Layered Double Hydroxides (LDH) as Delivery Vehicles of a Chimeric Protein Carrying Epitopes from the Porcine Reproductive and Respiratory Syndrome Virus

Alonso-Cerda,

García-Soto,

Miranda-López

et al. 2024

Pharmaceutics

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The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) causes reproductive failure and respiratory symptoms, leading to huge economic losses for the pig farming industry. Although several vaccines against PRRSV are available in the market; they show an overall low efficacy, and several countries have the need for vaccines covering the local, circulating variants. This project aims at developing a new chimeric antigen targeting specific epitopes from PRRSV and evaluating two test adjuvants to formulate a vaccine candidate. The test antigen was called LTB–PRRSV, which was produced recombinantly in Escherichia coli and consisted of the heat labile enterotoxin B subunit from E. coli (LTB) and four epitopes from PRRSV. LTB–PRRSV was rescued as inclusion bodies and methods for its solubilization, IMAC-based purification, and refolding were standardized, leading to mean yields of 18 mg of pure protein per liter culture. Layered double hydroxides (LDH) have been used as vaccine adjuvants given their biocompatibility, low cost, and positive surface charge that allows an efficient adsorption of negatively charged biomolecules. Therefore, LDH were selected as delivery vehicles of LTB–PRRSV. Pure LTB–PRRSV was adsorbed onto LDH by incubation at different LDH:LTB–PRRSV mass ratios (1:0.25, 1:0.5, 1:1, and 1:2) and at pH 9.5. The best adsorption occurred with a 1:2 mass ratio, and in a sucrose-tween solution. The conjugates obtained had a polydispersity index of 0.26, a hydrodynamic diameter of 192 nm, and a final antigen concentration of 64.2 μg/mL. An immunogenicity assessment was performed by injecting mice with LDH:LTB–PRRSV, Alum/LTB–PRRSV, or LTB–PRRSV in a scheme comprising three immunizations at two-week intervals and two dose levels (1 and 5 μg). LTB–PRRSV was capable of inducing strong humoral responses, which lasted for a longer period when LDH was used as the delivery vehicle/adjuvant. The potential of LDH to serve as an attractive carrier for veterinary vaccines is discussed.

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Section: Discussionsupporting

confidence: 85%

Layered Double Hydroxides (LDH) as Delivery Vehicles of a Chimeric Protein Carrying Epitopes from the Porcine Reproductive and Respiratory Syndrome Virus

Alonso-Cerda,

García-Soto,

Miranda-López

et al. 2024

Pharmaceutics

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“…The above two cytokines activate transcription factors that regulate the production of several defense molecules by natural killer cells, cytotoxic T cells, and macrophages (58)(59)(60). In addition, IFN-g cooperates with other factors, such as ChIL-17, to activate macrophages to kill phagocytized pathogens and infected cells (61) and promote immunoglobulin production. ChIFN-g also effectively induces, maintains, and links innate immunity to adaptive immune responses (62).…”

Section: Discussionmentioning

confidence: 99%

Probiotics Surface-Delivering Fiber2 Protein of Fowl Adenovirus 4 Stimulate Protective Immunity Against Hepatitis-Hydropericardium Syndrome in Chickens

et al. 2022

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Background and ObjectivesHepatitis-hydropericardium syndrome (HHS) caused by Fowl adenoviruses serotype 4 (FAdV-4) leads to severe economic losses to the poultry industry. Although various vaccines are available, vaccines that effectively stimulate intestinal mucosal immunity are still deficient. In the present study, novel probiotics that surface-deliver Fiber2 protein, the major virulence determiner and efficient immunogen for FAdV-4, were explored to prevent this fecal–oral-transmitted virus, and the induced protective immunity was evaluated after oral immunization.MethodsThe probiotic Enterococcus faecalis strain MDXEF-1 and Lactococcus lactis NZ9000 were used as host strains to deliver surface-anchoring Fiber2 protein of FAdV-4. Then the constructed live recombinant bacteria were orally vaccinated thrice with chickens at intervals of 2 weeks. Following each immunization, immunoglobulin G (IgG) in sera, secretory immunoglobulin A (sIgA) in jejunum lavage, immune-related cytokines, and T-cell proliferation were detected. Following challenge with the highly virulent FAdV-4, the protective effects of the probiotics surface-delivering Fiber2 protein were evaluated by verifying inflammatory factors, viral load, liver function, and survival rate.ResultsThe results demonstrated that probiotics surface-delivering Fiber2 protein stimulated humoral and intestinal mucosal immune responses in chickens, shown by high levels of sIgA and IgG antibodies, substantial rise in mRNA levels of cytokines, increased proliferative ability of T cells in peripheral blood, improved liver function, and reduced viral load in liver. Accordingly, adequate protection against homologous challenges and a significant increase in the overall survival rate were observed. Notably, chickens orally immunized with E. faecalis/DCpep-Fiber2-CWA were completely protected from the FAdV-4 challenge, which is better than L. lactis/DCpep-Fiber2-CWA.ConclusionThe recombinant probiotics surface-expressing Fiber2 protein could evoke remarkable humoral and cellular immune responses, relieve injury, and functionally damage target organs. The current study indicates a promising method used for preventing FAdV-4 infection in chickens.

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“…Interestingly, the protein expression of claudin 1 and occludin was increased in the BVDV-infected cells, but was decreased in the BVDV-infected cells treated with the indicated concentrations of gypenoside. The expression of the claudin 1 protein was markedly increased in the MDBK cells after the BVDV infection [28]. Claudin 1 and occludin are considered to be essential hepatitis C virus receptors or coreceptors in infected cells [29].…”

Section: Discussionmentioning

confidence: 99%

Gypenoside Inhibits Bovine Viral Diarrhea Virus Replication by Interfering with Viral Attachment and Internalization and Activating Apoptosis of Infected Cells

Yang

Zhang

Wang

et al. 2021

Viruses

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Bovine viral diarrhea virus (BVDV) causes a severe threat to the cattle industry due to ineffective control measures. Gypenoside is the primary component of Gynostemma pentaphyllum, which has potential medicinal value and has been widely applied as a food additive and herbal supplement. However, little is known about the antiviral effects of gypenoside. The present study aimed to explore the antiviral activities of gypenoside against BVDV infection. The inhibitory activity of gypenoside against BVDV was assessed by using virus titration and performing Western blotting, quantitative reverse transcription PCR (RT-qPCR), and immunofluorescence assays in MDBK cells. We found that gypenoside exhibited high anti-BVDV activity by interfering with the viral attachment to and internalization in cells. The study showed that BVDV infection inhibits apoptosis of infected cells from escaping the innate defense of host cells. Our data further demonstrated that gypenoside inhibited BVDV infection by electively activating the apoptosis of BVDV-infected cells for execution, as evidenced by the regulation of the expression of the apoptosis-related protein, promotion of caspase-3 activation, and display of positive TUNEL staining; no toxicity was observed in non-infected cells. Collectively, the data identified that gypenoside exerts an anti-BVDV-infection role by inhibiting viral attachment and internalization and selectively purging virally infected cells. Therefore, our study will contribute to the development of a novel prophylactic and therapeutic strategy against BVDV infection.

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Immunization with recombinant Erns-LTB fusion protein elicits protective immune responses against bovine viral diarrhea virus

Cited by 7 publications

References 31 publications

Layered Double Hydroxides (LDH) as Delivery Vehicles of a Chimeric Protein Carrying Epitopes from the Porcine Reproductive and Respiratory Syndrome Virus

Layered Double Hydroxides (LDH) as Delivery Vehicles of a Chimeric Protein Carrying Epitopes from the Porcine Reproductive and Respiratory Syndrome Virus

Probiotics Surface-Delivering Fiber2 Protein of Fowl Adenovirus 4 Stimulate Protective Immunity Against Hepatitis-Hydropericardium Syndrome in Chickens

Gypenoside Inhibits Bovine Viral Diarrhea Virus Replication by Interfering with Viral Attachment and Internalization and Activating Apoptosis of Infected Cells

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