Immunoinformatics analysis and in silico designing of a novel multi-epitope peptide vaccine against Staphylococcus aureus
Immunoinformatics analysis and in silico designing of a novel multi-epitope peptide vaccine against Staphylococcus aureus
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DOI：
10.1016/j.meegid.2016.12.010
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发表时间：
2017-03-01
影响因子：
3.2
通讯作者：
Ghasemi, Younes
中科院分区：
文献类型：
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作者：
Hajighahramani, Nasim;Nezafat, Navid;Ghasemi, Younes
金黄色葡萄球菌是一种引起人类多种感染的病原体。耐甲氧西林表皮葡萄金黄色葡萄球菌是一种耐药性形式，是医院内葡萄球菌感染的原因，其在健康人群中的频率正在增加。因此，需要开发新的技术来克服这种细菌感染。在这方面，使用疫苗控制感染是一种适当的替代办法。本研究利用免疫信息学方法分析了三种抗原决定簇作为候选疫苗，并设计了一种新型的多表位疫苗，以诱导针对沙门氏菌的细胞、体液和天然免疫应答。金黄色。选择α-烯醇化酶、凝集因子A和铁表面决定簇B作为保护性抗原，并应用酚可溶性调节蛋白α 4作为佐剂。使用各种免疫信息学服务器对每种抗原进行表位鉴定。此外，我们的蛋白疫苗的三级结构进行了预测和验证。随后，将最佳建模的蛋白质结构用于细化过程。然后将改进的模型应用于与Toll样受体2（TLR 2）的对接研究。在下一步中，使用分子动力学（MD）模拟来评估疫苗分子和TLR 2-疫苗复合物的稳定性。从所提及的抗原中选择高排序的表位。选择的表位和佐剂通过适当的接头融合在一起。然后，选择并验证了模型化的蛋白质结构。验证结果表明，初始模型需要细化。经过优化过程，最终模型生成。最后，选择疫苗与TLR 2复合物的最佳对接模型。本研究试图设计一种能有效激发体液免疫和细胞免疫应答的亚单位疫苗。因此，我们希望我们设计的疫苗可以击败耐药葡萄球菌感染。(C)2016爱思唯尔B. V.保留所有权利。
Staphylococcus aureus is a pathogen that causes a variety of infections in humans. Methicillin-resistant S. aureus, which is an antibiotic-resistant form, is responsible for nosocomial staphylococcal infections, whose frequency is increasing in healthy people. Thereby, the development of novel techniques is required to overcome this bacterial infection. In this context, the use of vaccines to control infections is an appropriate alternative. In this study, immunoinformatics analysis is used on three antigenic determinants as vaccine candidates, and a novel multi-epitope vaccine is designed to induce cellular, humoral, and innate immune responses against S. aureus. Alpha-enolase, clumping factor A, and iron surface determinant B were selected as the protective antigens; and phenol-soluble modulin alpha 4was applied as the adjuvant. Epitopes identification was done for each antigen using various immunoinformatics servers. Moreover, the tertiary structure of our protein vaccine was predicted and validated. Subsequently, the best-modeled protein structure was used for the refinement process. There fined model was then applied for docking studies with Toll-like receptor 2 (TLR2). In the next step, molecular dynamics (MD) simulation was used to evaluate the stability of vaccine molecule and TLR2-vaccine complex. The high ranked epitopes were selected from the mentioned antigens. The selected epitopes and the adjuvant were fused together by proper linkers. Then, the modeled protein structure was selected and validated. Validation results indicated that the initial model needs refinement. After a refinement process, the final model was generated. Finally, the best docked model of vaccine and TLR2 complex was selected. In this research, we attempted to design an efficient subunit vaccine, which could stimulate humoral and cellular immune responses. Therefore, we expect that our designed vaccine could defeat antibiotic-resistant staphylococcal infections. (C) 2016 Elsevier B.V. All rights reserved.