Damfo Shymaa Abdullah, Reche Pedro, Gatherer Derek, Flower Darren R
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.
J Mol Graph Model. 2017 Nov;78:195-205. doi: 10.1016/j.jmgm.2017.10.004. Epub 2017 Oct 12.
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%.
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%。