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...

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Main Authors: Ji-Hoon Park, Min-Hee Kim, Edwin Sutanto, Seok-Won Na, Min-Jae Kim, Joon Sup Yeom, Myat Htut Nyunt, Mohammed Mohieldien Abbas Elfaki, Muzamil Mahdi Abdel Hamid, Seok Ho Cha, Sisay Getachew Alemu, Kanlaya Sriprawat, Nicholas M Anstey, Matthew J Grigg, Bridget E Barber, Timothy William, Qi Gao, Yaobao Liu, Richard D Pearson, Ric N Price, Francois Nosten, Sung-Il Yoon, Joo Hwan No, Eun-Taek Han, Sarah Auburn, Bruce Russell, Jin-Hee Han
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-06-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://doi.org/10.1371/journal.pntd.0010492
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author Ji-Hoon Park
Min-Hee Kim
Edwin Sutanto
Seok-Won Na
Min-Jae Kim
Joon Sup Yeom
Myat Htut Nyunt
Mohammed Mohieldien Abbas Elfaki
Muzamil Mahdi Abdel Hamid
Seok Ho Cha
Sisay Getachew Alemu
Kanlaya Sriprawat
Nicholas M Anstey
Matthew J Grigg
Bridget E Barber
Timothy William
Qi Gao
Yaobao Liu
Richard D Pearson
Ric N Price
Francois Nosten
Sung-Il Yoon
Joo Hwan No
Eun-Taek Han
Sarah Auburn
Bruce Russell
Jin-Hee Han
author_facet Ji-Hoon Park
Min-Hee Kim
Edwin Sutanto
Seok-Won Na
Min-Jae Kim
Joon Sup Yeom
Myat Htut Nyunt
Mohammed Mohieldien Abbas Elfaki
Muzamil Mahdi Abdel Hamid
Seok Ho Cha
Sisay Getachew Alemu
Kanlaya Sriprawat
Nicholas M Anstey
Matthew J Grigg
Bridget E Barber
Timothy William
Qi Gao
Yaobao Liu
Richard D Pearson
Ric N Price
Francois Nosten
Sung-Il Yoon
Joo Hwan No
Eun-Taek Han
Sarah Auburn
Bruce Russell
Jin-Hee Han
author_sort Ji-Hoon Park
collection DOAJ
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.
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spelling doaj.art-3436a76552fa4fde89759ad3b0038c8a2023-01-13T05:32:50ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352022-06-01166e001049210.1371/journal.pntd.0010492Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity.Ji-Hoon ParkMin-Hee KimEdwin SutantoSeok-Won NaMin-Jae KimJoon Sup YeomMyat Htut NyuntMohammed Mohieldien Abbas ElfakiMuzamil Mahdi Abdel HamidSeok Ho ChaSisay Getachew AlemuKanlaya SriprawatNicholas M AnsteyMatthew J GriggBridget E BarberTimothy WilliamQi GaoYaobao LiuRichard D PearsonRic N PriceFrancois NostenSung-Il YoonJoo Hwan NoEun-Taek HanSarah AuburnBruce RussellJin-Hee HanPlasmodium 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.https://doi.org/10.1371/journal.pntd.0010492
spellingShingle Ji-Hoon Park
Min-Hee Kim
Edwin Sutanto
Seok-Won Na
Min-Jae Kim
Joon Sup Yeom
Myat Htut Nyunt
Mohammed Mohieldien Abbas Elfaki
Muzamil Mahdi Abdel Hamid
Seok Ho Cha
Sisay Getachew Alemu
Kanlaya Sriprawat
Nicholas M Anstey
Matthew J Grigg
Bridget E Barber
Timothy William
Qi Gao
Yaobao Liu
Richard D Pearson
Ric N Price
Francois Nosten
Sung-Il Yoon
Joo Hwan No
Eun-Taek Han
Sarah Auburn
Bruce Russell
Jin-Hee Han
Geographical distribution and genetic diversity of Plasmodium vivax reticulocyte binding protein 1a correlates with patient antigenicity.
PLoS Neglected Tropical Diseases
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
url https://doi.org/10.1371/journal.pntd.0010492
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