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Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity
Plasmodium vivax is the most widespread cause of human malaria. Recent reports of drug resistant vivax malaria and the challenge of eradicating the dormant liver forms increase the importance of vaccine development against this relapsing disease. P. vivax reticulocyte binding protein 1a (PvRBP1a) is...
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/PMC9258880/ https://www.ncbi.nlm.nih.gov/pubmed/35737709 http://dx.doi.org/10.1371/journal.pntd.0010492 |
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author | Park, Ji-Hoon Kim, Min-Hee Sutanto, Edwin Na, Seok-Won Kim, Min-Jae Yeom, Joon Sup Nyunt, Myat Htut Abbas Elfaki, Mohammed Mohieldien Abdel Hamid, Muzamil Mahdi Cha, Seok Ho Alemu, Sisay Getachew Sriprawat, Kanlaya Anstey, Nicholas M. Grigg, Matthew J. Barber, Bridget E. William, Timothy Gao, Qi Liu, Yaobao Pearson, Richard D. Price, Ric N. Nosten, Francois Yoon, Sung-Il No, Joo Hwan Han, Eun-Taek Auburn, Sarah Russell, Bruce Han, Jin-Hee |
author_facet | Park, Ji-Hoon Kim, Min-Hee Sutanto, Edwin Na, Seok-Won Kim, Min-Jae Yeom, Joon Sup Nyunt, Myat Htut Abbas Elfaki, Mohammed Mohieldien Abdel Hamid, Muzamil Mahdi Cha, Seok Ho Alemu, Sisay Getachew Sriprawat, Kanlaya Anstey, Nicholas M. Grigg, Matthew J. Barber, Bridget E. William, Timothy Gao, Qi Liu, Yaobao Pearson, Richard D. Price, Ric N. Nosten, Francois Yoon, Sung-Il No, Joo Hwan Han, Eun-Taek Auburn, Sarah Russell, Bruce Han, Jin-Hee |
author_sort | Park, Ji-Hoon |
collection | PubMed |
description | Plasmodium vivax is the most widespread cause of human malaria. Recent reports of drug resistant vivax malaria and the challenge of eradicating the dormant liver forms increase the importance of vaccine development against this relapsing disease. P. vivax reticulocyte binding protein 1a (PvRBP1a) is a potential vaccine candidate, which is involved in red cell tropism, a crucial step in the merozoite invasion of host reticulocytes. As part of the initial evaluation of the PvRBP1a vaccine candidate, we investigated its genetic diversity and antigenicity using geographically diverse clinical isolates. We analysed pvrbp1a genetic polymorphisms using 202 vivax clinical isolates from six countries. Pvrbp1a was separated into six regions based on specific domain features, sequence conserved/polymorphic regions, and the reticulocyte binding like (RBL) domains. In the fragmented gene sequence analysis, PvRBP1a region II (RII) and RIII (head and tail structure homolog, 152–625 aa.) showed extensive polymorphism caused by random point mutations. The haplotype network of these polymorphic regions was classified into three clusters that converged to independent populations. Antigenicity screening was performed using recombinant proteins PvRBP1a-N (157–560 aa.) and PvRBP1a-C (606–962 aa.), which contained head and tail structure region and sequence conserved region, respectively. Sensitivity against PvRBP1a-N (46.7%) was higher than PvRBP1a-C (17.8%). PvRBP1a-N was reported as a reticulocyte binding domain and this study identified a linear epitope with moderate antigenicity, thus an attractive domain for merozoite invasion-blocking vaccine development. However, our study highlights that a global PvRBP1a-based vaccine design needs to overcome several difficulties due to three distinct genotypes and low antigenicity levels. |
format | Online Article Text |
id | pubmed-9258880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92588802022-07-07 Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity Park, Ji-Hoon Kim, Min-Hee Sutanto, Edwin Na, Seok-Won Kim, Min-Jae Yeom, Joon Sup Nyunt, Myat Htut Abbas Elfaki, Mohammed Mohieldien Abdel Hamid, Muzamil Mahdi Cha, Seok Ho Alemu, Sisay Getachew Sriprawat, Kanlaya Anstey, Nicholas M. Grigg, Matthew J. Barber, Bridget E. William, Timothy Gao, Qi Liu, Yaobao Pearson, Richard D. Price, Ric N. Nosten, Francois Yoon, Sung-Il No, Joo Hwan Han, Eun-Taek Auburn, Sarah Russell, Bruce Han, Jin-Hee PLoS Negl Trop Dis Research Article Plasmodium vivax is the most widespread cause of human malaria. Recent reports of drug resistant vivax malaria and the challenge of eradicating the dormant liver forms increase the importance of vaccine development against this relapsing disease. P. vivax reticulocyte binding protein 1a (PvRBP1a) is a potential vaccine candidate, which is involved in red cell tropism, a crucial step in the merozoite invasion of host reticulocytes. As part of the initial evaluation of the PvRBP1a vaccine candidate, we investigated its genetic diversity and antigenicity using geographically diverse clinical isolates. We analysed pvrbp1a genetic polymorphisms using 202 vivax clinical isolates from six countries. Pvrbp1a was separated into six regions based on specific domain features, sequence conserved/polymorphic regions, and the reticulocyte binding like (RBL) domains. In the fragmented gene sequence analysis, PvRBP1a region II (RII) and RIII (head and tail structure homolog, 152–625 aa.) showed extensive polymorphism caused by random point mutations. The haplotype network of these polymorphic regions was classified into three clusters that converged to independent populations. Antigenicity screening was performed using recombinant proteins PvRBP1a-N (157–560 aa.) and PvRBP1a-C (606–962 aa.), which contained head and tail structure region and sequence conserved region, respectively. Sensitivity against PvRBP1a-N (46.7%) was higher than PvRBP1a-C (17.8%). PvRBP1a-N was reported as a reticulocyte binding domain and this study identified a linear epitope with moderate antigenicity, thus an attractive domain for merozoite invasion-blocking vaccine development. However, our study highlights that a global PvRBP1a-based vaccine design needs to overcome several difficulties due to three distinct genotypes and low antigenicity levels. Public Library of Science 2022-06-23 /pmc/articles/PMC9258880/ /pubmed/35737709 http://dx.doi.org/10.1371/journal.pntd.0010492 Text en © 2022 Park 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 Park, Ji-Hoon Kim, Min-Hee Sutanto, Edwin Na, Seok-Won Kim, Min-Jae Yeom, Joon Sup Nyunt, Myat Htut Abbas Elfaki, Mohammed Mohieldien Abdel Hamid, Muzamil Mahdi Cha, Seok Ho Alemu, Sisay Getachew Sriprawat, Kanlaya Anstey, Nicholas M. Grigg, Matthew J. Barber, Bridget E. William, Timothy Gao, Qi Liu, Yaobao Pearson, Richard D. Price, Ric N. Nosten, Francois Yoon, Sung-Il No, Joo Hwan Han, Eun-Taek Auburn, Sarah Russell, Bruce Han, Jin-Hee Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity |
title | Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity |
title_full | Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity |
title_fullStr | Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity |
title_full_unstemmed | Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity |
title_short | Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity |
title_sort | geographical distribution and genetic diversity of plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258880/ https://www.ncbi.nlm.nih.gov/pubmed/35737709 http://dx.doi.org/10.1371/journal.pntd.0010492 |
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