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设计一种新型 EmTSP-3 和 EmTIP 基于多表位疫苗针对 感染。

Design of a novel EmTSP-3 and EmTIP based multi-epitope vaccine against infection.

机构信息

State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China.

出版信息

Front Immunol. 2024 Sep 16;15:1425603. doi: 10.3389/fimmu.2024.1425603. eCollection 2024.

Abstract

BACKGROUND

Current treatments and prevention strategies for echinococcosis are inadequate. Recent advancements in molecular vaccine development show promise against ; however, remains a challenge. A Multi-epitope Vaccine could potentially induce specific B and T lymphocyte responses, thereby offering protection against infection.

METHODS

This study aimed to develop a MEV against alveolar echinococcosis. Key epitopes from the proteins EmTSP3 and EmTIP were identified using immunoinformatics analyses. These analyses were conducted to assess the MEV feasibility, structural characteristics, molecular docking, molecular dynamics simulations, and immune simulations. The immunogenicity and antigenicity of the vaccine were evaluated through and experiments, employing ELISA, Western blotting, FCM, challenge infection experiments, and ELISPOT.

RESULTS

The effective antigenicity and immunogenicity of MEV were demonstrated through immunoinformatics, as well as and experiments. experiments revealed that MEV increased the secretion of IFN-γ and IL-4 in PBMC and successfully bound to specific antibodies in patient serum. Furthermore, mice immunized with MEV developed a robust immune response, characterized by elevated levels of CD4+ and CD8+ T-cells, increased secretion of IFN-γ and IL-4 by specific Th1 and Th2 cells, and heightened serum antibody levels. Importantly, MEV reduced the weight of cysts by conferring resistance against echinococcosis. These findings suggest that MEV is a promising candidate for the prevention of infection.

CONCLUSION

A total of 7 CTL, 7 HTL, 5 linear B-cell, and 2 conformational B-cell epitopes were identified. The vaccine has demonstrated effective antigenicity and immunogenicity against AE through molecular docking, immune simulation, molecular dynamics studies, and both and experiments. It provides effective protection against infection, thereby laying a foundation for further development.

摘要

背景

目前针对包虫病的治疗和预防策略并不完善。最近分子疫苗开发方面的进展显示出针对棘球蚴病的希望,但仍存在挑战。多表位疫苗有可能诱导特异性 B 和 T 淋巴细胞反应,从而提供针对棘球蚴感染的保护。

方法

本研究旨在开发一种针对泡型包虫病的 MEV。使用免疫信息学分析鉴定 EmTSP3 和 EmTIP 蛋白中的关键表位。进行这些分析是为了评估 MEV 的可行性、结构特征、分子对接、分子动力学模拟和免疫模拟。通过 ELISA、Western blot、FCM、挑战感染实验和 ELISPOT 实验评估疫苗的免疫原性和抗原性。

结果

通过免疫信息学以及 和 实验证明了 MEV 的有效抗原性和免疫原性。 实验表明,MEV 增加了 PBMC 中 IFN-γ 和 IL-4 的分泌,并成功结合了患者血清中的特异性抗体。此外,用 MEV 免疫的小鼠产生了强大的免疫反应,表现为 CD4+和 CD8+T 细胞水平升高,特异性 Th1 和 Th2 细胞分泌 IFN-γ 和 IL-4 增加,以及血清抗体水平升高。重要的是,MEV 通过赋予对包虫病的抵抗力来减轻囊肿的重量。这些发现表明 MEV 是预防棘球蚴感染的有前途的候选物。

结论

共鉴定出 7 个 CTL、7 个 HTL、5 个线性 B 细胞和 2 个构象 B 细胞表位。该疫苗通过分子对接、免疫模拟、分子动力学研究以及 和 实验,显示出针对 AE 的有效抗原性和免疫原性。它为棘球蚴感染提供了有效的保护,为进一步的开发奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b84a/11439721/bf58285606df/fimmu-15-1425603-g002.jpg

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