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


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%.

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Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: © 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Funding: grants BIO2014:54164-R and Inmunotek S.L.
Uncontrolled Keywords: Vaccine design ,MHC binding prediction ,population coverage ,malaria
Publication ISSN: 1873-4243
Last Modified: 08 Dec 2023 10:31
Date Deposited: 13 Oct 2017 07:45
Full Text Link: http://www.scie ... 093326317305430
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PURE Output Type: Article
Published Date: 2017-11
Published Online Date: 2017-10-12
Accepted Date: 2017-10-05
Authors: Damfo, Shymaa Abdullah
Reche, Pedro A.
Gatherer, Derek
Flower, Darren R (ORCID Profile 0000-0002-8542-7067)

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