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

Damfo, Shymaa Abdullah and Reche, Pedro and Gatherer, Derek and Flower, Darren R. (2017) In silico design of knowledge-based Plasmodium falciparum epitope ensemble vaccines. Journal of Molecular Graphics and Modelling, 78. pp. 195-205. ISSN 1093-3263

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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%.

Item Type:
Journal Article
Journal or Publication Title:
Journal of Molecular Graphics and Modelling
Additional Information:
This is the author’s version of a work that was accepted for publication in Journal of Molecular Graphics and Modelling. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Molecular Graphics and Modelling, 78, 2017 DOI: 10.1016/j.jmgm.2017.10.004
Uncontrolled Keywords:
?? vaccine designmhc binding predictionpopulation coveragemalariamaterials chemistryspectroscopyphysical and theoretical chemistrycomputer graphics and computer-aided design ??
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Deposited On:
17 Oct 2017 08:22
Last Modified:
31 Dec 2023 00:52