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Analysis of Putative Epitope Candidates of Mycobacterium tuberculosis Against Pakistani Human Leukocyte Antigen Background: An Immunoinformatic Study for the Development of Future Vaccine.
International Journal of Peptide Research and Therapeutics ( IF 2.5 ) Pub Date : 2020-09-04 , DOI: 10.1007/s10989-020-10111-w
Malik Siddique Mahmood 1 , Duaa Bin-T-Abid 1 , Saba Irshad 1 , Hina Batool 2
Affiliation  

Tuberculosis (TB), a chronic disease caused by Mycobacterium tuberculosis (Mtb), is a global health issue across the world. Pakistan ranks fifth among the countries, which are facing, a significantly great number of mortalities and morbidities due to TB. Unfortunately, all previously reported treatments are not successful for the eradication of TB. Here in this study, we report an emerging treatment option for this disease. We have applied immunoinformatics to predict highly conserved B and T-cell epitopes from Mtb, showing significant binding affinities to the frequent HLA alleles in the Pakistani population. A total of ten highly referenced and experimentally validated epitopes were selected from the Immune Epitope Database (IEDB), followed by their conservancy analysis using weblogos. The consensus sequences and variants derived from these sequences were examined, for their binding affinities, with prevalent HLA alleles of Pakistan. Moreover, the antigenic and allergenic natures of these peptides were also evaluated via Vaxijen and AllerTOP, respectively. Consequently, all potentially allergenic and non-antigenic, peptide fragments, were excluded from the analysis. Among all putative epitopes, three CD8 + T-cell epitopes were selected, as ideal vaccine candidates and, population coverage analysis revealed that the combination of these three peptides was covering, 67.28% Pakistani Asian and 57.15% mixed Pakistani populations. Likewise, eleven linear and six conformational or discontinuous B-cell epitopes were also marked as potential vaccine candidates based on their prediction score, non-allergenic nature, and antigenic properties. These epitopes, however, need the final validation via wet-lab studies. After their approval, these epitopes would be effective candidates for the future designing of epitope-based vaccines against Mtb infections in Pakistan.



中文翻译:

对巴基斯坦人类白细胞抗原背景的结核分枝杆菌推定表位候选者的分析:未来疫苗开发的免疫信息学研究。

结核病 (TB) 是一种由结核分枝杆菌 (Mtb)引起的慢性疾病 ,是世界范围内的全球性健康问题。巴基斯坦在面临大量结核病死亡率和发病率的国家中排名第五。不幸的是,以前报道的所有治疗方法都不能成功根除结核病。在这项研究中,我们报告了一种针对这种疾病的新兴治疗选择。我们已经应用免疫信息学来预测来自Mtb的高度保守的 B 和 T 细胞表位,显示出与常见HLA的显着结合亲和力巴基斯坦人群中的等位基因。从免疫表位数据库 (IEDB) 中选择了总共十个高度引用和实验验证的表位,然后使用 weblogos 对其进行保守性分析。对源自这些序列的共有序列和变体进行了检查,以了解它们与普遍HLA的结合亲和力巴基斯坦的等位基因。此外,还分别通过 Vaxijen 和 AllerTOP 评估了这些肽的抗原性和过敏性。因此,所有潜在的过敏性和非抗原性肽片段都被排除在分析之外。在所有推定的表位中,选择了三个 CD8 + T 细胞表位作为理想的候选疫苗,群体覆盖分析显示这三个肽的组合覆盖了 67.28% 的巴基斯坦亚洲人和 57.15% 的巴基斯坦混合人群。同样,11 个线性和 6 个构象或不连续的 B 细胞表位也根据其预测分数、非过敏性和抗原特性被标记为潜在的候选疫苗。然而,这些表位需要通过湿实验室研究进行最终验证。在他们同意后,巴基斯坦的Mtb感染。

更新日期:2020-09-05
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