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Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens
Investigation of the diversity of malaria parasite antigens can help prioritize and validate them as vaccine candidates and identify the most common variants for inclusion in vaccine formulations. Studies of vaccine candidates of the most virulent human malaria parasite, Plasmodium falciparum, have...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843232/ https://www.ncbi.nlm.nih.gov/pubmed/35108259 http://dx.doi.org/10.1371/journal.pcbi.1009801 |
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author | Naung, Myo T. Martin, Elijah Munro, Jacob Mehra, Somya Guy, Andrew J. Laman, Moses Harrison, G. L. Abby Tavul, Livingstone Hetzel, Manuel Kwiatkowski, Dominic Mueller, Ivo Bahlo, Melanie Barry, Alyssa E. |
author_facet | Naung, Myo T. Martin, Elijah Munro, Jacob Mehra, Somya Guy, Andrew J. Laman, Moses Harrison, G. L. Abby Tavul, Livingstone Hetzel, Manuel Kwiatkowski, Dominic Mueller, Ivo Bahlo, Melanie Barry, Alyssa E. |
author_sort | Naung, Myo T. |
collection | PubMed |
description | Investigation of the diversity of malaria parasite antigens can help prioritize and validate them as vaccine candidates and identify the most common variants for inclusion in vaccine formulations. Studies of vaccine candidates of the most virulent human malaria parasite, Plasmodium falciparum, have focused on a handful of well-known antigens, while several others have never been studied. Here we examine the global diversity and population structure of leading vaccine candidate antigens of P. falciparum using the MalariaGEN Pf3K (version 5.1) resource, comprising more than 2600 genomes from 15 malaria endemic countries. A stringent variant calling pipeline was used to extract high quality antigen gene ‘haplotypes’ from the global dataset and a new R-package named VaxPack was used to streamline population genetic analyses. In addition, a newly developed algorithm that enables spatial averaging of selection pressure on 3D protein structures was applied to the dataset. We analysed the genes encoding 23 leading and novel candidate malaria vaccine antigens including csp, trap, eba175, ama1, rh5, and CelTOS. Our analysis shows that current malaria vaccine formulations are based on rare haplotypes and thus may have limited efficacy against natural parasite populations. High levels of diversity with evidence of balancing selection was detected for most of the erythrocytic and pre-erythrocytic antigens. Measures of natural selection were then mapped to 3D protein structures to predict targets of functional antibodies. For some antigens, geographical variation in the intensity and distribution of these signals on the 3D structure suggests adaptation to different human host or mosquito vector populations. This study provides an essential framework for the diversity of P. falciparum antigens to be considered in the design of the next generation of malaria vaccines. |
format | Online Article Text |
id | pubmed-8843232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88432322022-02-15 Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens Naung, Myo T. Martin, Elijah Munro, Jacob Mehra, Somya Guy, Andrew J. Laman, Moses Harrison, G. L. Abby Tavul, Livingstone Hetzel, Manuel Kwiatkowski, Dominic Mueller, Ivo Bahlo, Melanie Barry, Alyssa E. PLoS Comput Biol Research Article Investigation of the diversity of malaria parasite antigens can help prioritize and validate them as vaccine candidates and identify the most common variants for inclusion in vaccine formulations. Studies of vaccine candidates of the most virulent human malaria parasite, Plasmodium falciparum, have focused on a handful of well-known antigens, while several others have never been studied. Here we examine the global diversity and population structure of leading vaccine candidate antigens of P. falciparum using the MalariaGEN Pf3K (version 5.1) resource, comprising more than 2600 genomes from 15 malaria endemic countries. A stringent variant calling pipeline was used to extract high quality antigen gene ‘haplotypes’ from the global dataset and a new R-package named VaxPack was used to streamline population genetic analyses. In addition, a newly developed algorithm that enables spatial averaging of selection pressure on 3D protein structures was applied to the dataset. We analysed the genes encoding 23 leading and novel candidate malaria vaccine antigens including csp, trap, eba175, ama1, rh5, and CelTOS. Our analysis shows that current malaria vaccine formulations are based on rare haplotypes and thus may have limited efficacy against natural parasite populations. High levels of diversity with evidence of balancing selection was detected for most of the erythrocytic and pre-erythrocytic antigens. Measures of natural selection were then mapped to 3D protein structures to predict targets of functional antibodies. For some antigens, geographical variation in the intensity and distribution of these signals on the 3D structure suggests adaptation to different human host or mosquito vector populations. This study provides an essential framework for the diversity of P. falciparum antigens to be considered in the design of the next generation of malaria vaccines. Public Library of Science 2022-02-02 /pmc/articles/PMC8843232/ /pubmed/35108259 http://dx.doi.org/10.1371/journal.pcbi.1009801 Text en © 2022 Naung et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Naung, Myo T. Martin, Elijah Munro, Jacob Mehra, Somya Guy, Andrew J. Laman, Moses Harrison, G. L. Abby Tavul, Livingstone Hetzel, Manuel Kwiatkowski, Dominic Mueller, Ivo Bahlo, Melanie Barry, Alyssa E. Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens |
title | Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens |
title_full | Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens |
title_fullStr | Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens |
title_full_unstemmed | Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens |
title_short | Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens |
title_sort | global diversity and balancing selection of 23 leading plasmodium falciparum candidate vaccine antigens |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843232/ https://www.ncbi.nlm.nih.gov/pubmed/35108259 http://dx.doi.org/10.1371/journal.pcbi.1009801 |
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