A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

Wang, Jingbo; Su, Chuanyou; Liu, Rui; Liu, Baoxiu; Khan, Inam Ullah; Xie, Jun; Zhu, Nianyong

doi:10.1371/journal.pone.0170313

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…Figure 3 (Additional file 1 : Table S6) indicates that there is no significant ( p > 0.05) increase across all the treatment groups on day 14 (after the primer dose). This is in consonance with the works of Wang et al [ 42 ], which showed a slow IgG production after the first immunization. Day 21 (7 days after the first booster dose indicated a significant ( p < 0.05) increase when 2DHBV + ESM immunized mice were compared to mice immunized with the Hepatitis B vaccine.…”

Section: Discussionsupporting

confidence: 92%

Could eggshell membrane be an adjuvant for recombinant Hepatitis B vaccine?: A preliminary investigation

et al. 2023

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Background Despite the invasiveness of the Hepatitis B infection, its vaccines are only formulated with FDA-approved alum-based adjuvants, which poorly elicit a lasting immune response, hence the need for a more effective adjuvant system. This study evaluated the immunogenicity and toxicity of eggshell membranes (ESM) when administered as an adjuvant for the recombinant HBV vaccine (rHBsAg) in albino mice. Differential white blood cell analysis, as well as the titer measurement of Immunoglobulin G, subclass G1 and G2a on indirect ELISA, was performed to measure the immune-modulatory potentials of ESM. Moreover, analysis of the liver marker enzyme (AST and ALT) and body/liver weights was performed to ascertain the toxicity level of ESM. Finally, Immuno-informatic analysis was used to investigate the immune-modulatory potential of individual member proteins of ESM. Results Our results showed a significant improvement in the experimental group's lymphocyte count after boost-dose administration compared to the controls, whereas there was no significant change in the granulocyte population. Furthermore, the formulations (ESM-rHBsAg) significantly improved IgG and IgG1 titers after each successive immunization. Body/liver weight and liver function showed ESM non-toxic to mice. The immunoinformatic analysis discovered ovalbumin, lysozyme-C, and UFM-1 as the member proteins of ESM with immune-modulatory activities of activating antigen-presenting cells (APC). Conclusion This study has provided a clue into the potential valorization of eggshell membranes and their peptides as an adjuvant for vaccines such as HBV. We recommend more in-depth molecular analysis to support our findings as well as foster real-life application.

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Section: Discussionsupporting

confidence: 92%

Could eggshell membrane be an adjuvant for recombinant Hepatitis B vaccine?: A preliminary investigation

et al. 2023

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“…Therefore, HBsAg likely regulates NK cells during CHB infection by inhibiting STAT3 dimerization, nuclear translocation, or DNA binding. The secreted protein SBP and mitochondrial protein ECHS1 have been previously reported to be the binding proteins of HBsAg, but the NK cell membrane binding protein(s) of HBsAg remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

STAT3 directly regulates NKp46 transcription in NK cells of HBeAg-negative CHB patients

Zheng

Yang

Han

et al. 2019

Journal of Leukocyte Biology

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NK cells play an important role in early control of HBV infection. The function of NK cells is inhibited in chronic hepatitis B virus (CHB) infection, although the underlying mechanism remains unknown. We found that the expression of STAT3 decreased in peripheral NK cells of CHB patients, and was associated with low levels of degranulation and IFN-secretion. In addition, STAT3 levels were positively correlated with cytolysis-associated molecules and antiviral cytokines, such as CD107a, granzyme B, perforin, and IFN-. HBsAg directly inhibited the expression and activation of STAT3 in NK cells, and knocking down STAT3 expression in NK cells inhibited proliferation, decreased cyclin d1 levels, and suppressed responsiveness to IL-21 stimulation.Furthermore, STAT3 directly bound to the promoter of NKp46, an important activating receptor of NK cells, to regulate its transcription and expression. Taken together, our findings indicate that STAT3 is an important positive regulator of NK cells, and provide a new mechanism of NK cell dysfunction in CHB. K E Y W O R D SCD107a, CHB, granzyme B, IFN-, natural killer cells, NKp46, perforin, STAT3 INTRODUCTIONChronic hepatitis B virus (HBV) infection is a major health problem worldwide, and can trigger a wide spectrum of liver diseases such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), which are altogether responsible for approximately 1 million deaths annually. 1 The aims of anti-chronic HBV (CHB) therapy are persistent suppression of viral replication, and the prevention of fibrotic progression and oncogenesis. 2 CHB is divided into the hepatitis B envelope Ag (HBeAg)-positive and HBeAg-negative phases. 2 The HBeAg + patients have demonstrated immune tolerance, and HBeAg seroconversion used to be the ideal endpoint of CHB therapy. 3,4 However, recent studies indicate that the HBeAg − CHB patients, including the inactive hepatitis B surface Ag (HBsAg) carriers, have a high risk of progressing to HCC, 5,6 and do not show any immune regulatory mechanism. 2 NK cells are crucial mediators of the innate immune system, and respond to viral infection rapidly without Ag presentation via the Abbreviations: CHB, chronic hepatitis B virus; EGF, epidermal growth factor; HBeAg, hepatitis B envelope Ag; HBsAg, hepatitis B surface Ag; HD, healthy donor; HGF, hepatocyte growth factor; HIES, hyper-IgE syndrome. MHC. 7,8 NK cell functions are regulated by several surface recognition receptors, with both activating and inhibitory functions, 9 which need to be maintained in a balanced state for proper NK cell response. Blocking the activating receptors NKp46 and DNAM-1 impaired NK cell cytotoxicity against cytomegalovirus-infected M s. 10 In CHB patients, the levels of activating receptors such as 2B4 and NKG2D were reduced by TGF-, while that of the inhibitory receptor NKG2A was elevated, resulting in dysfunctional IFN-production and NK cell cytotoxicity. 11-13 HBsAg sero-clearance by pegylated-IFN -2a and nucleos(t)ide analogues restored NK cell function in the HBeAgnegative ...

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Nonclinical safety and immunogenicity assessment of a combined DTacP vaccine in animal models

Li,

Fu,

et al. 2024

J of Applied Toxicology

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The (diphtheria, tetanus, and pertussis [acellular, component] [DTacP]) vaccine is a combined vaccine designed to prevent three potentially fatal diseases including pertussis, tetanus, and diphtheria in both children and adults. We utilized advanced technology to develop a novel DTacP vaccine that was previously unavailable in China. The nonclinical studies were performed to evaluate the immunogenicity, potential toxicity, and local tolerance of the vaccine in animal models. In the immunogenicity study, three batches of the vaccine were intraperitoneally administered to National Institutes of Health (NIH) mice, resulting in 100% seropositivity for all three batches. Additionally, antibody levels notably increased as the immunization dosage increased. In acute toxicity study, no mortality was observed among the animals during the 14‐day observation period, and no abnormalities in clinical signs were reported. Active systemic anaphylaxis assessment in guinea pigs showed no evidence of serious allergic reactions in the vaccine groups. In the repeat‐dose toxicity study, where five intramuscular doses were administered every 2 weeks, gross autopsy and histopathological examination revealed no vaccine‐related systemic pathological changes in rats, with dose site irritant reactions mostly recovered at the end of recovery period. In conclusion, the vaccine demonstrated good local and systemic tolerance, supporting its clinical development.

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A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

Cited by 4 publications

References 26 publications

Could eggshell membrane be an adjuvant for recombinant Hepatitis B vaccine?: A preliminary investigation

Could eggshell membrane be an adjuvant for recombinant Hepatitis B vaccine?: A preliminary investigation

STAT3 directly regulates NKp46 transcription in NK cells of HBeAg-negative CHB patients

Nonclinical safety and immunogenicity assessment of a combined DTacP vaccine in animal models

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