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Title: Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity
Authors: Jin Hee Han
Jee Sun Cho
Jessica J.Y. Ong
Ji Hoon Park
Myat Htut Nyunt
Edwin Sutanto
Hidayat Trimarsanto
Beyene Petros
Abraham Aseffa
Sisay Getachew
Kanlaya Sriprawat
Nicholas M. Anstey
Matthew J. Grigg
Bridget E. Barber
Timothy William
Gao Qi
Yaobao Liu
Richard D. Pearson
Sarah Auburn
Ric N. Price
Francois Nosten
Laurent Rénia
Bruce Russell
Eun Taek Han
The Jenner Institute
A-Star, Singapore Immunology Network
Medical College of Soochow University
Jiangsu Institute of Parasitic Diseases
Armauer Hansen Research Institute
Addis Ababa University
Eijkman Institute for Molecular Biology
Shoklo Malaria Research Unit
Menzies School of Health Research
University of Otago
Mahidol University
Nuffield Department of Medicine
Wellcome Sanger Institute
University of Oxford Medical Sciences Division
Kangwon National University
Gleneagles Hospital
Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit
Queen Elizabeth Hospital
Keywords: Medicine
Issue Date: 1-Jul-2020
Citation: PLoS Neglected Tropical Diseases. Vol.14, No.7 (2020), 1-16
Abstract: © 2020 Han et al. Plasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key objective for the control and elimination of vivax malaria. Erythrocyte binding-like (EBL) protein family mem-bers such as Duffy binding protein (PvDBP) are of critical importance to erythrocyte invasion and have been the major target for vivax malaria vaccine development. In this study, we focus on another member of EBL protein family, P. vivax erythrocyte binding protein (PvEBP). PvEBP was first identified in Cambodian (C127) field isolates and has subse-quently been showed its preferences for binding reticulocytes which is directly inhibited by antibodies. We analysed PvEBP sequence from 316 vivax clinical isolates from eight coun-tries including China (n = 4), Ethiopia (n = 24), Malaysia (n = 53), Myanmar (n = 10), Papua New Guinea (n = 16), Republic of Korea (n = 10), Thailand (n = 174), and Vietnam (n = 25). PvEBP gene exhibited four different phenotypic clusters based on the insertion/deletion (indels) variation. PvEBP-RII (179–479 aa.) showed highest polymorphism similar to other EBL family proteins in various Plasmodium species. Whereas even though PvEBP-RIII-V (480–690 aa.) was the most conserved domain, that showed strong neutral selection pressure for gene purifying with significant population expansion. Antigenicity of both of PvEBP-RII (16.1%) and PvEBP-RIII-V (21.5%) domains were comparatively lower than other P. vivax antigen which expected antigens associated with merozoite invasion. Total IgG recognition level of PvEBP-RII was stronger than PvEBP-RIII-V domain, whereas total IgG inducing level was stronger in PvEBP-RIII-V domain. These results suggest that PvEBP-RII is mainly recognized by natural IgG for innate protection, whereas PvEBP-RIII-V stimulates IgG production activity by B-cell for acquired immunity. Overall, the low antigenic-ity of both regions in patients with vivax malaria likely reflects genetic polymorphism for strong positive selection in PvEBP-RII and purifying selection in PvEBP-RIII-V domain. These observations pose challenging questions to the selection of EBP and point out the importance of immune pressure and polymorphism required for inclusion of PvEBP as a vaccine candidate.
ISSN: 19352735
Appears in Collections:Scopus 2020

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