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针对印度丙型肝炎病毒3a基因型的T细胞和B细胞表位鉴定用于疫苗开发——一项计算机模拟分析

Identification of T cell and B cell epitopes against Indian HCV-genotype-3a for vaccine development- An in silico analysis.

作者信息

Chauhan Varun, Singh Mini P, Ratho Radha K

机构信息

Department of Virology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, Punjab 160012, India.

Department of Virology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, Punjab 160012, India.

出版信息

Biologicals. 2018 May;53:63-71. doi: 10.1016/j.biologicals.2018.02.003. Epub 2018 Mar 5.

DOI:10.1016/j.biologicals.2018.02.003
PMID:29519752
Abstract

Hepatitis C virus (HCV) infects almost 150 million people and is a leading cause of liver disease worldwide. It has been classified into seven genotypes; the most common genotype affecting Indian population is genotype 3 (60-70%). Currently there is no vaccine for any genotype of HCV. In order to develop peptide based vaccine against HCV, it is important to identify the conservancy in the circulating genotypes, along with the Human Leucocyte Antigen (HLA) alleles in the target population. The present study aims to identify conserved CD4 and CD8 T cells and B cell epitopes against Indian HCV-genotype-3a using an in silico analysis. In the present study, 28 promiscuous CD4 T cell epitopes and some CD8 epitopes were identified. The NS4 region was predicted to be the most antigenic with maximum number of conserved and promiscuous CD4 T cell epitopes and CD8 T cell epitopes having strong and intermediate affinity towards a number of HLA alleles prevalent in Indian population. Additionally, some linear B cell epitopes were also identified, which could generate neutralizing antibodies. In order to ascertain the binding pattern of the identified epitopes with HLA alleles, molecular docking analysis was carried out. The authors suggest further experimental validation to investigate the immunogenicity of the identified epitopes.

摘要

丙型肝炎病毒(HCV)感染了近1.5亿人,是全球肝病的主要病因。它已被分为七种基因型;影响印度人群的最常见基因型是3型(60%-70%)。目前尚无针对任何HCV基因型的疫苗。为了开发基于肽的HCV疫苗,识别循环基因型中的保守性以及目标人群中的人类白细胞抗原(HLA)等位基因非常重要。本研究旨在通过计算机分析识别针对印度HCV 3a基因型的保守CD4和CD8 T细胞以及B细胞表位。在本研究中,鉴定出28个混杂的CD4 T细胞表位和一些CD8表位。NS4区域被预测为抗原性最强的区域,具有最多的保守和混杂CD4 T细胞表位以及对印度人群中多种流行的HLA等位基因具有强亲和力和中等亲和力的CD8 T细胞表位。此外,还鉴定出一些线性B细胞表位,它们可产生中和抗体。为了确定所鉴定表位与HLA等位基因的结合模式,进行了分子对接分析。作者建议进一步进行实验验证,以研究所鉴定表位的免疫原性。

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