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从寨卡病毒基因组中发现 T 细胞驱动的亚单位疫苗:一种免疫信息学方法。

Discovery of T-cell Driven Subunit Vaccines from Zika Virus Genome: An Immunoinformatics Approach.

机构信息

Biomedical Informatics Centre, National Institute of Pathology-ICMR, New Delhi, 110029, India.

Bioinformatics Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, 442102, India.

出版信息

Interdiscip Sci. 2017 Dec;9(4):468-477. doi: 10.1007/s12539-017-0238-3. Epub 2017 Nov 1.

Abstract

The recent outbreaks of Zika virus and the absence of a specific therapy have necessitated to identify T-cell-stimulating antigenic peptides as potential subunit vaccine candidates. The translated ssRNA (+) genome of Zika virus was explored in EMBOSS antigenic and VaxiJen to predict 63 peptides as potential antigens. Three MHC-II binding peptide prediction tools, viz. NetMHCIIpan, PREDIVAC and immune epitope database (IEDB) were employed in consensus on 63 antigenic peptides to propose 14 T-helper cell epitopes. Similarly, analysis on 63 antigenic peptides through NetMHC, NetCTL and IEDB MHC-I binding peptide prediction tool led to identification of 14 CTL epitopes. Seven T-cell epitopes, C:44-66, M:135-149, NS2A:124-144, NS3:421-453, NS3:540-554, NS4B:90-134 and NS4B:171-188, are observed to share overlapping MHC-I and MHC-II binding motifs and hence, are being proposed to constitute minimum T-cell antigens to elicit protective T-cell immune response against Zika. Three of them, C:44-66, NS3:421-453 and NS3:540-554 are identified to be conserved across all the selected strains of Zika virus. Moreover, the 21 T-cell epitopes are non-self to humans and exhibited good coverage in variable populations of 14 geographical locations. Therefore, 21 T-cell epitopes are proposed as potential subunit vaccines against Zika virus.

摘要

最近爆发的寨卡病毒和缺乏特定疗法的情况下,有必要确定 T 细胞刺激抗原肽作为潜在的亚单位疫苗候选物。在 EMBOSS 抗原和 VaxiJen 中探索了寨卡病毒的翻译 ssRNA(+)基因组,以预测 63 个可能作为潜在抗原的肽。使用了三种 MHC-II 结合肽预测工具,即 NetMHCIIpan、PREDIVAC 和免疫表位数据库 (IEDB),对 63 个抗原肽进行共识分析,提出了 14 个 T 辅助细胞表位。同样,通过 NetMHC、NetCTL 和 IEDB MHC-I 结合肽预测工具对 63 个抗原肽进行分析,确定了 14 个 CTL 表位。观察到七个 T 细胞表位,C:44-66、M:135-149、NS2A:124-144、NS3:421-453、NS3:540-554、NS4B:90-134 和 NS4B:171-188,它们具有重叠的 MHC-I 和 MHC-II 结合基序,因此被提议构成最小的 T 细胞抗原,以引发针对寨卡的保护性 T 细胞免疫反应。其中三个表位,C:44-66、NS3:421-453 和 NS3:540-554,被鉴定为在所有选定的寨卡病毒株中保守。此外,这 21 个 T 细胞表位对人类是非自身的,并且在 14 个地理位置的不同人群中具有良好的覆盖率。因此,提出了 21 个 T 细胞表位作为针对寨卡病毒的潜在亚单位疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed03/7091030/2a478f21c5b3/12539_2017_238_Fig1_HTML.jpg

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