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蛋壳膜能否作为重组乙型肝炎疫苗的佐剂?一项初步调查。

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

作者信息

Joshua Parker Elijah, Ilo Charity Chinyere, Ukachukwu Uzochukwu Gospel, Odimegwu Damian Chukwu, Asomadu Rita Onyekachukwu, Ezeorba Timothy Prince Chidike

机构信息

Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, 410001 Enugu State Nigeria.

Department of Pharmaceutical Microbiology and Biotechnology, University of Nigeria, Nsukka, 410001 Enugu State Nigeria.

出版信息

Futur J Pharm Sci. 2023;9(1):28. doi: 10.1186/s43094-023-00481-5. Epub 2023 Apr 5.

Abstract

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.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s43094-023-00481-5.

摘要

背景

尽管乙型肝炎感染具有侵袭性,但其疫苗仅使用美国食品药品监督管理局(FDA)批准的铝基佐剂配制,这种佐剂难以引发持久的免疫反应,因此需要更有效的佐剂系统。本研究评估了卵壳膜(ESM)作为重组乙肝疫苗(rHBsAg)佐剂在白化小鼠体内的免疫原性和毒性。通过差异白细胞分析以及间接酶联免疫吸附测定(ELISA)法检测免疫球蛋白G、亚类G1和G2a的滴度,以测量ESM的免疫调节潜力。此外,分析肝脏标记酶(谷草转氨酶和谷丙转氨酶)以及体重/肝脏重量,以确定ESM的毒性水平。最后,采用免疫信息学分析来研究ESM单个成员蛋白的免疫调节潜力。

结果

我们的结果显示,与对照组相比,实验组在加强剂量给药后淋巴细胞计数有显著改善,而粒细胞数量没有显著变化。此外,每次连续免疫后,制剂(ESM-rHBsAg)显著提高了IgG和IgG1滴度。体重/肝脏重量和肝功能显示ESM对小鼠无毒。免疫信息学分析发现卵清蛋白、溶菌酶-C和UFM-1是ESM的成员蛋白,具有激活抗原呈递细胞(APC)的免疫调节活性。

结论

本研究为卵壳膜及其肽作为乙肝等疫苗佐剂的潜在价值提供了线索。我们建议进行更深入的分子分析以支持我们的发现,并促进实际应用。

补充信息

在线版本包含可在10.1186/s43094-023-00481-5获取的补充材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f71/10074367/463b8706f5a3/43094_2023_481_Fig1_HTML.jpg

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