Enterococcus faecium is an emerging ESKAPE bacterium that is capable of causing severe public health complications in humans. There are currently no licensed treatments or vaccinations to combat the deadly pathogen. We aimed to design a potent and novel prophylactic chimeric vaccine against E. faecium through an immunoinformatics approach The antigenic Penicillin-binding protein 5 (PBP 5) protein was selected to identify B and T cell epitopes, followed by conservancy analysis, population coverage, physiochemical assessment, secondary and tertiary structural analysis. Using various immunoinformatics methods and tools, two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes were finally selected for vaccine development. The constructed vaccine was determined to be highly immunogenic, cytokine-producing, antigenic, non-toxic, non-allergenic, and stable, as well as potentially effective against E. faecium. In addition, disulfide engineering, codon adaptation, and in silico cloning, were used to improve stability and expression efficiency in the host E. coli. Molecular docking and molecular dynamics simulations indicated that the structure of the vaccine is stable and has a high affinity for the TLR4 receptor. The immune simulation results revealed that both B and T cells had an increased response to the vaccination component. Conclusively, the in-depth in silico analysis suggests, the proposed vaccine to elicit a robust immune response against E. faecium infection and hence a promising target for further experimental trials.

中文翻译：

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设计一种新型多表位疫苗，以引起对致病性耐多药屎肠球菌的强烈免疫反应

粪肠球菌是一种新兴的 ESKAPE 细菌，能够引起人类严重的公共卫生并发症。目前还没有获得许可的治疗方法或疫苗来对抗这种致命的病原体。我们旨在通过免疫信息学方法设计一种针对粪肠球菌的有效且新型的预防性嵌合疫苗选择抗原性青霉素结合蛋白 5 (PBP 5) 蛋白来鉴定 B 和 T 细胞表位，然后进行保守性分析、群体覆盖、理化评估，二级和三级结构分析。使用各种免疫信息学方法和工具，最终选择了两个线性 B 细胞表位、五个 CTL 表位和两个 HTL 表位用于疫苗开发。构建的疫苗被确定为具有高度免疫原性、细胞因子产生、抗原性、无毒、非过敏性，稳定，以及对 E. faecium 可能有效。此外，二硫键工程、密码子适应和计算机克隆被用于提高宿主大肠杆菌中的稳定性和表达效率。分子对接和分子动力学模拟表明，疫苗结构稳定，对TLR4受体具有高亲和力。免疫模拟结果显示，B 细胞和 T 细胞对疫苗成分的反应都增强了。最后，深入的计算机分析表明，所提出的疫苗可引发针对粪肠球菌感染的强大免疫反应，因此是进一步实验试验的有希望的目标。用于提高宿主大肠杆菌中的稳定性和表达效率。分子对接和分子动力学模拟表明，疫苗结构稳定，对TLR4受体具有高亲和力。免疫模拟结果显示，B 细胞和 T 细胞对疫苗成分的反应都增强了。最后，深入的计算机分析表明，所提出的疫苗可引发针对粪肠球菌感染的强大免疫反应，因此是进一步实验试验的有希望的目标。用于提高宿主大肠杆菌中的稳定性和表达效率。分子对接和分子动力学模拟表明，疫苗结构稳定，对TLR4受体具有高亲和力。免疫模拟结果显示，B 细胞和 T 细胞对疫苗成分的反应都增强了。最后，深入的计算机分析表明，所提出的疫苗可引发针对粪肠球菌感染的强大免疫反应，因此是进一步实验试验的有希望的目标。免疫模拟结果显示，B 细胞和 T 细胞对疫苗成分的反应都增强了。最后，深入的计算机分析表明，所提出的疫苗可引发针对粪肠球菌感染的强大免疫反应，因此是进一步实验试验的有希望的目标。免疫模拟结果显示，B 细胞和 T 细胞对疫苗成分的反应都增强了。最后，深入的计算机分析表明，所提出的疫苗可引发针对粪肠球菌感染的强大免疫反应，因此是进一步实验试验的有希望的目标。