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藻酸盐纳米粒包被的多表位蛋白疫苗作为志贺氏菌疫苗候选物。

A multi-epitope protein vaccine encapsulated in alginate nanoparticles as a candidate vaccine against Shigella sonnei.

机构信息

Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran.

Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran.

出版信息

Sci Rep. 2024 Sep 28;14(1):22484. doi: 10.1038/s41598-024-73105-4.

Abstract

Shigellosis, caused by the Gram-negative bacterium Shigella, is a major global health challenge. Despite extensive research over the past two decades, no commercial vaccine is available to prevent Shigella infection. Developing multi-epitope vaccines offers a promising and innovative approach to tackling infectious diseases. In this study, we produced a multi-epitope vaccine candidate using E. coli BL21 (DE3) plysS bacteria and purified the vaccine protein with Ni-NTA affinity chromatography. We then prepared alginate nanoparticles containing the vaccine protein, with a particle size of 122 ± 6 nm, PDI 0.17, SPAN 0.83, and zeta potential of -27 ± 2 mV. Successful protein loading was confirmed through nanodrop and ATR-FTIR analyses. To evaluate the immunogenicity of the encapsulated vaccine, mice were orally vaccinated, and their serum was analyzed for IgG, IL-4, and IFN-γ levels cytokines. The results showed a significant increase in IgG level in the vaccinated group compared to controls. Additionally, the vaccinated group exhibited a notable increase in IL-4 and IFN-γ cytokines, indicating a robust Th-cell-mediated immune response essential for combating Shigella. Our nano-vaccine demonstrated high efficacy in activating both humoral and cellular immunity, effectively protecting against the bacteria. The alginate-based oral vaccine candidate thus emerges as a promising strategy for developing a multi-epitope vaccine candidate against Shigella.

摘要

志贺氏菌病是由革兰氏阴性细菌志贺氏菌引起的,是一个全球性的主要健康挑战。尽管在过去的二十年中进行了广泛的研究,但目前尚无商业疫苗可用于预防志贺氏菌感染。开发多表位疫苗为应对传染病提供了一种有前途和创新的方法。在这项研究中,我们使用大肠杆菌 BL21(DE3)plyss 细菌生产了一种多表位疫苗候选物,并通过 Ni-NTA 亲和层析纯化了疫苗蛋白。然后,我们制备了含有疫苗蛋白的海藻酸钠纳米颗粒,其粒径为 122±6nm,PDI 为 0.17,SPAN 为 0.83,zeta 电位为-27±2mV。通过纳米滴和 ATR-FTIR 分析证实了蛋白的成功加载。为了评估包封疫苗的免疫原性,我们对小鼠进行了口服免疫接种,并分析了其血清中的 IgG、IL-4 和 IFN-γ 细胞因子水平。结果表明,与对照组相比,接种组的 IgG 水平显著升高。此外,接种组的 IL-4 和 IFN-γ 细胞因子明显增加,表明针对志贺氏菌的强大 Th 细胞介导的免疫反应。我们的纳米疫苗在激活体液和细胞免疫方面表现出很高的功效,有效地保护免受细菌感染。因此,基于海藻酸钠的口服疫苗候选物成为开发针对志贺氏菌的多表位疫苗候选物的一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f066/11438873/2198209d09dc/41598_2024_73105_Fig1_HTML.jpg

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