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用于基孔肯雅热疫苗开发的印度常见频率 HLA I 类等位基因与 cTAP 结合肽结合模式的研究。

Study of the Binding Pattern of HLA Class I Alleles of Indian Frequency and cTAP Binding Peptide for Chikungunya Vaccine Development.

作者信息

Saxena Prashant, Mishra Sanjay

机构信息

Department of Biotechnology, K. S. Vira College of Engineering & Management, Bijnor, UP(W) 246701 India.

School of Biotechnology, IFTM University, Delhi Road (NH 24), Moradabad, UP(W) 244102 India.

出版信息

Int J Pept Res Ther. 2020;26(4):2437-2448. doi: 10.1007/s10989-020-10038-2. Epub 2020 Feb 3.

Abstract

Chikungunya is a mosquito-borne disease, caused by the member of the family belongs to the genus , making it a major threat in all developing countries as well as some developed countries. The mosquito acts as a vector for the disease and carries the CHIK-Virus. To date there is no direct treatment available and that demands the development of more effective vaccines. In this study author employed Immune Epitope Database and Analysis Resource, a machine learning-based algorithm principally working on the Artificial Neural Network (ANN) algorithm, also known as (IEDB-ANN) for the prediction and analysis of Epitopes. A total of 173 epitopes were identified on the basis of IC50 values, among them 40 epitopes were found, sharing part with the linear B-cell epitopes and exposed to the cTAP1protein, and out of 40, 6 epitopes were noticed to show interactions with the cTAP with their binding energy ranging from - 3.61 to - 1.22 kcal/mol. The six epitopes identified were exposed to the HLA class I alleles and from this all revealed interaction with the HLA alleles and minimum binding energy that ranges from - 4.12 to - 5.88 kcal/mol. Besides, two T cell epitopes i.e. KVFTGVYPE and STVPVAPPR were found most promiscuous candidates. These promiscuous epitopes-HLA complexes were further analyzed by the molecular dynamics simulation to check the stability of the complex. Results obtained from this study suggest that the identified epitopes i.e. and , are likely to be capable of passing through the lumen of ER to bind withthe HLA class I allele and provide new insights and potential application in the designing and development of peptide-based vaccine candidate for the treatment of chikungunya.

摘要

基孔肯雅热是一种由属于 属的家族成员引起的蚊媒疾病,这使其在所有发展中国家以及一些发达国家构成重大威胁。蚊子作为该疾病的传播媒介,携带基孔肯雅病毒(CHIK-Virus)。迄今为止,尚无直接可用的治疗方法,这就需要研发更有效的疫苗。在本研究中,作者采用了免疫表位数据库和分析资源(Immune Epitope Database and Analysis Resource),这是一种主要基于人工神经网络(ANN)算法的机器学习算法,也称为(IEDB-ANN),用于表位的预测和分析。基于IC50值共鉴定出173个表位,其中发现40个表位与线性B细胞表位部分重叠,并暴露于cTAP1蛋白,在这40个表位中,有6个表位被发现与cTAP相互作用,其结合能范围为 -3.61至 -1.22千卡/摩尔。鉴定出的6个表位暴露于HLA I类等位基因,并且所有这些表位都显示出与HLA等位基因的相互作用以及范围为 -4.12至 -5.88千卡/摩尔的最小结合能。此外,发现两个T细胞表位即KVFTGVYPE和STVPVAPPR是最具多态性的候选表位。通过分子动力学模拟进一步分析这些多态性表位 - HLA复合物,以检查复合物的稳定性。本研究获得的结果表明,鉴定出的表位即 和 ,可能能够穿过内质网腔与HLA I类等位基因结合,并为设计和开发用于治疗基孔肯雅热的基于肽的候选疫苗提供新的见解和潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1ba/7223317/e09ccd738929/10989_2020_10038_Fig1_HTML.jpg

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