Reverse immunodynamics: a new method for identifying targets of protective immunity
File(s)
Author(s)
Type
Journal Article
Abstract
Despite a dramatic increase in our ability to catalogue variation among pathogen genomes, we have made far fewer advances in using this information to identify targets of protective immunity. Epidemiological models predict that strong immune selection can cause antigenic variants to structure into genetically discordant sets of antigenic types (e.g. serotypes). A corollary of this theory is that targets of immunity may be identified by searching for non-overlapping associations of amino acids among co-circulating antigenic variants. We propose a novel population genetics methodology that combines such predictions with phylogenetic analyses to identify genetic loci (epitopes) under strong immune selection. We apply this concept to the AMA-1 protein of the malaria parasite Plasmodium falciparum and find evidence of epitopes among certain regions of low variability which could render them ideal vaccine candidates. The proposed method can be applied to a myriad of multi-strain pathogens for which vast amounts of genetic data has been collected in recent years.
Date Issued
2019-02-15
Date Acceptance
2018-11-20
Citation
Scientific Reports, 2019, 9, pp.1-8
ISSN
2045-2322
Publisher
Nature Portfolio
Start Page
1
End Page
8
Journal / Book Title
Scientific Reports
Volume
9
Copyright Statement
© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000458752600016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
AMA1
APICAL MEMBRANE ANTIGEN-1
DOMAIN-III
EVOLUTION
GENE
INHIBITORY ANTIBODIES
MALARIA VACCINE CANDIDATE
Multidisciplinary Sciences
PLASMODIUM
Science & Technology
Science & Technology - Other Topics
STRAIN STRUCTURE
SURFACE-PROTEINS
Publication Status
Published
Article Number
ARTN 2164
Date Publish Online
2019-02-15