Computational Medicinal Chemistry Laboratory, Department of Chemistry, UCSS, Abdul Wali Khan University, Mardan, Pakistan.
State Key Laboratories of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Curr Pharm Des. 2023;29(19):1504-1515. doi: 10.2174/1381612829666230418104520.
Borrelia burgdorferi is regarded as an extremely dangerous bacteria causing infectious disease in humans, resulting in musculoskeletal pain, fatigue, fever and cardiac symptom. Because of all alarming concerns, no such prophylaxis setup has been available against Borrelia burgdorferi till now. In fact, vaccine construction using traditional methods is so expensive and time-consuming. Therefore, considering all concerns, we designed a multi-epitope-based vaccine design against Borrelia burgdorferi using in silico approaches.
To design an effective and safe vaccine that can activate cell-mediated and humoral immunity against Borrelia burgdorferi by using various bioinformatics tools.
The present study utilized different computational methodologies, covering different ideas and elements in bioinformatics tools. The protein sequence of Borrelia burgdorferi was retrieved from the NCBI database. Different B and T cell epitopes were predicated using the IEDB tool. Efficient B and T cell epitopes were further assessed for vaccine construction using linkers AAY, EAAAK and GPGPG, respectively. Furthermore, the tertiary structure of constructed vaccine was predicated, and its interaction was determined with TLR9 using ClusPro software. In addition, further atomic level detail of docked complex and their immune response were further determined by MD simulation and C-ImmSim tool, respectively.
A protein with immunogenic potential and good vaccine properties (candidate) was identified based on high binding scores, low percentile rank, non-allergenicity and good immunological properties, which were further used to calculate epitopes. Additionally, molecular docking possesses strong interaction; seventeen H-bonds interactions were reported, such as THR101-GLU264, THR185-THR270, ARG 257-ASP210, ARG 257-ASP 210, ASP259-LYS 174, ASN263-GLU237, CYS 265-GLU 233, CYS 265-TYR 197, GLU267- THR202, GLN 270-THR202, TYR345-ASP 210, TYR345-THR 213, ARG 346-ASN209, SER350- GLU141, SER350-GLU141, ASP 424-ARG220 and ARG426-THR216 with TLR-9. Finally, high expression was determined in E. coli (CAI = (0.9045), and GC content = (72%)). Using the IMOD server, all-atom MD simulations of docked complex affirmed its significant stability. The outcomes of immune simulation indicate that both T and B cells represent a strong response to the vaccination component.
This type of in-silico technique may precisely decrease valuable time and expenses in vaccine designing against Borrelia burgdorferi for experimental planning in laboratories. Currently, scientists frequently utilize bioinformatics approaches that speed up their vaccine-based lab work.
伯氏疏螺旋体被认为是一种极其危险的细菌，会导致人类传染病，引起肌肉骨骼疼痛、疲劳、发热和心脏症状。由于所有这些令人担忧的问题，目前还没有针对伯氏疏螺旋体的预防措施。事实上，使用传统方法构建疫苗既昂贵又耗时。因此，考虑到所有这些问题，我们使用基于多种表位的方法设计了一种针对伯氏疏螺旋体的疫苗。
使用各种生物信息学工具设计一种针对伯氏疏螺旋体的有效且安全的疫苗，以激活针对伯氏疏螺旋体的细胞介导和体液免疫。
本研究利用了不同的计算方法，涵盖了生物信息学工具中的不同想法和元素。从 NCBI 数据库中检索到伯氏疏螺旋体的蛋白质序列。使用 IEDB 工具预测不同的 B 和 T 细胞表位。使用接头 AAY、EAAAK 和 GPGPG 进一步评估有效的 B 和 T 细胞表位，用于疫苗构建。此外，预测构建疫苗的三级结构，并使用 ClusPro 软件确定其与 TLR9 的相互作用。此外，通过 MD 模拟和 C-ImmSim 工具进一步确定对接复合物的原子级细节及其免疫反应。
根据高结合评分、低百分位秩、非变应原性和良好的免疫特性，确定了一种具有免疫原性和良好疫苗特性的蛋白质（候选物），并进一步用于计算表位。此外，分子对接具有很强的相互作用；报告了十七个氢键相互作用，如 THR101-GLU264、THR185-THR270、ARG 257-ASP210、ARG 257-ASP 210、ASP259-LYS 174、ASN263-GLU237、CYS 265-GLU 233、CYS 265-TYR 197、GLU267-THR202、GLN 270-THR202、TYR345-ASP 210、TYR345-THR 213、ARG 346-ASN209、SER350-GLU141、SER350-GLU141、ASP 424-ARG220 和 ARG426-THR216 与 TLR-9。最后，在大肠杆菌中确定了高表达（CAI =（0.9045），GC 含量=（72%））。使用 IMOD 服务器对对接复合物进行全原子 MD 模拟证实了其显著的稳定性。免疫模拟的结果表明，T 细胞和 B 细胞都对疫苗成分产生强烈反应。
这种基于计算机的技术可能会显著缩短针对伯氏疏螺旋体的疫苗设计在实验室中的宝贵时间和费用。目前，科学家经常使用生物信息学方法来加快他们基于疫苗的实验室工作。
