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

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

Research output: Contribution to journalArticle

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%.
Original languageEnglish
JournalJournal of Molecular Graphics and Modelling
VolumeEarly online
Early online date12 Oct 2017
DOIs
Publication statusE-pub ahead of print - 12 Oct 2017

Bibliographical note

© 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/.

Funding: grants BIO2014:54164-R and Inmunotek S.L.

Keywords

  • Vaccine design
  • MHC binding prediction
  • population coverage
  • malaria

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