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基于沙门氏菌发病因子的嵌合疫苗构建体的计算机设计与免疫信息学分析。

In silico design and immunoinformatics analysis of a chimeric vaccine construct based on Salmonella pathogenesis factors.

机构信息

Research Center for Health Technology Assessment and Medical Informatics, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

出版信息

Microb Pathog. 2023 Jul;180:106130. doi: 10.1016/j.micpath.2023.106130. Epub 2023 Apr 28.

Abstract

Currently, there are two vaccines based on killed and/or weakened Salmonella bacteria, but no recombinant vaccine is available for preventing or treating the disease. We used an in silico approach to design a multi-epitope vaccine against Salmonella using OmpA, OmpS, SopB, SseB, SthA and FilC antigens. We predicted helper T lymphocyte, cytotoxic T lymphocyte, and IFN-γ epitopes. The FilC sequence was used as a bovine TLR5 agonist, and the linkers KK, AAY, GPGPG and EAAAK were used to connect epitopes. The final sequence consisted of 747 amino acid residues, and the expressed soluble protein (∼79.6 kDa) was predicted to be both non-allergenic and antigenic. The tertiary structure of modeled protein was refined and validated, and the interactions of vaccine 3D structure were evaluated using molecular docking, and molecular dynamics simulation (RMSD, RMSF and Gyration). This structurally stable protein could interact with human TLR5. The C-ImmSim server predicted that this proposed vaccine likely induces an immune response by stimulating T and B cells, making it a potential candidate for further evaluation for the prevention and treatment of Salmonella infection.

摘要

目前,有两种基于灭活和/或减毒沙门氏菌的疫苗,但没有重组疫苗可用于预防或治疗这种疾病。我们使用计算机方法设计了一种针对沙门氏菌的多表位疫苗,该疫苗使用了 OmpA、OmpS、SopB、SseB、SthA 和 FilC 抗原。我们预测了辅助性 T 淋巴细胞、细胞毒性 T 淋巴细胞和 IFN-γ 表位。FilC 序列被用作牛 TLR5 激动剂,连接子 KK、AAY、GPGPG 和 EAAAK 用于连接表位。最终序列由 747 个氨基酸残基组成,预测表达的可溶性蛋白(∼79.6 kDa)既无过敏原性又有抗原性。对模型蛋白的三级结构进行了细化和验证,并使用分子对接和分子动力学模拟(RMSD、RMSF 和旋转)评估了疫苗 3D 结构的相互作用。这种结构稳定的蛋白可以与人 TLR5 相互作用。C-ImmSim 服务器预测,这种拟议的疫苗通过刺激 T 细胞和 B 细胞很可能诱导免疫反应,使其成为预防和治疗沙门氏菌感染的进一步评估的潜在候选物。

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