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基于知识的恶性疟原虫表位组合疫苗的计算机辅助设计

In silico design of knowledge-based Plasmodium falciparum epitope ensemble vaccines.

作者信息

Damfo Shymaa Abdullah, Reche Pedro, Gatherer Derek, Flower Darren R

机构信息

School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, United Kingdom.

Immunomedicine Group, Facultad de Medicina, Departamento de Microbiologia I, Universidad Complutense de Madrid, Madrid, Spain.

出版信息

J Mol Graph Model. 2017 Nov;78:195-205. doi: 10.1016/j.jmgm.2017.10.004. Epub 2017 Oct 12.

Abstract

Malaria is a global health burden, and a major cause of mortality and morbidity in Africa. Here we designed a putative malaria epitope ensemble vaccine by selecting an optimal set of pathogen epitopes. From the IEDB database, 584 experimentally-verified CD8+ epitopes and 483 experimentally-verified CD4+ epitopes were collected; 89% of which were found in 8 proteins. Using the PVS server, highly conserved epitopes were identified from variability analysis of multiple alignments of Plasmodium falciparum protein sequences. The allele-dependent binding of epitopes was then assessed using IEDB analysis tools, from which the population protection coverage of single and combined epitopes was estimated. Ten conserved epitopes from four well-studied antigens were found to have a coverage of 97.9% of the world population: 7 CD8+ T cell epitopes (LLMDCSGSI, FLIFFDLFLV, LLACAGLAYK, TPYAGEPAPF, LLACAGLAY, SLKKNSRSL, and NEVVVKEEY) and 3 CD4+ T cell epitopes (MRKLAILSVSSFLFV, KSKYKLATSVLAGLL and GLAYKFVVPGAATPYE). The addition of four heteroclitic peptides - single point mutated epitopes - increased HLA binding affinity and raised the predicted world population coverage above 99%.

摘要

疟疾是一项全球卫生负担,也是非洲地区死亡率和发病率的主要成因。在此,我们通过挑选一组最佳的病原体表位,设计了一种假定的疟疾表位组合疫苗。从国际免疫信息数据库(IEDB)中,收集了584个经实验验证的CD8+表位和483个经实验验证的CD4+表位;其中89%存在于8种蛋白质中。使用PVS服务器,通过对恶性疟原虫蛋白质序列的多序列比对进行变异性分析,确定了高度保守的表位。然后使用IEDB分析工具评估表位的等位基因依赖性结合情况,据此估计单个表位和组合表位的群体保护覆盖率。发现来自四种深入研究抗原的10个保守表位覆盖了全球97.9%的人口:7个CD8+ T细胞表位(LLMDCSGSI、FLIFFDLFLV、LLACAGLAYK、TPYAGEPAPF、LLACAGLAY、SLKKNSRSL和NEVVVKEEY)和3个CD4+ T细胞表位(MRKLAILSVSSFLFV、KSKYKLATSVLAGLL和GLAYKFVVPGAATPYE)。添加四种异质性肽——单点突变表位——提高了HLA结合亲和力,并使预测的全球人口覆盖率超过99%。

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