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

Journal of Molecular Graphics & Modelling
Shymaa Abdullah DamfoDarren R Flower

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%.

Citations

Jun 23, 2018·Chemical Biology & Drug Design·David MurphyDarren R Flower
Jan 9, 2019·Frontiers in Immunology·Silvia Sánchez-RamónJosé Luis Subiza
Dec 12, 2019·Frontiers in Immunology·Lucas Michel-TodóJulio Alonso-Padilla
Dec 12, 2019·BMC Bioinformatics·Monica J QuinzoPedro A Reche

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