Structural patterns of selection and diversity for Plasmodium vivax antigens DBP and AMA1
Abstract Background Plasmodium vivax is a significant contributor to the global malaria burden, and a vaccine targeting vivax malaria is urgently needed. An understanding of the targets of functional immune responses during the course of natural infection will aid in the development of a vaccine. An...
| Published in: | Malaria Journal |
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| Main Authors: | , , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
BMC
2018
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| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-018-2324-3 https://doaj.org/article/8367d7e10ff74f0abf59cd139abf4b8c |
| Summary: | Abstract Background Plasmodium vivax is a significant contributor to the global malaria burden, and a vaccine targeting vivax malaria is urgently needed. An understanding of the targets of functional immune responses during the course of natural infection will aid in the development of a vaccine. Antibodies play a key role in this process, with responses against particular epitopes leading to immune selection pressure on these epitopes. A number of techniques exist to estimate levels of immune selection pressure on particular epitopes, with a sliding window analysis often used to determine particular regions likely to be under immune pressure. However, such analysis neglects protein three-dimensional structural information. With this in mind, a newly developed tool, BioStructMap, was applied to two key antigens from Plasmodium vivax: PvAMA1 and PvDBP Region II. This tool incorporates structural information into tests of selection pressure. Results Sequences from a number of populations were analysed, examining spatially-derived nucleotide diversity and Tajima’s D over protein structures for PvAMA1 and PvDBP. Structural patterns of nucleotide diversity were similar across all populations examined, with Domain I of PvAMA1 having the highest nucleotide diversity and displaying significant signatures of immune selection pressure (Tajima’s D > 0). Nucleotide diversity for PvDBP was highest bordering the dimerization and DARC-binding interface, although there was less evidence of immune selection pressure on PvDBP compared with PvAMA1. This study supports previous work that has identified Domain I as the main target of immune-mediated selection pressure for PvAMA1, and also supports studies that have identified functional epitopes within PvDBP Region II. Conclusions The BioStructMap tool was applied to leading vaccine candidates from P. vivax, to examine structural patterns of selection and diversity across a number of geographic populations. There were striking similarities in structural patterns of diversity ... |
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