Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity
Year: 2020
Type: article
Abstract: 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 members 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 subsequently been showed its preferences for binding reticulocytes which is directly inhibited by antibodies. We analysed PvEBP sequence from 316 vivax clinical isolates from eight countries 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 antigenicity 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.
Source: PLoS neglected tropical diseases
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
Institutions: Kangwon National University, University of Otago, Agency for Science, Technology and Research, Singapore Immunology Network, Jenner Institute, Eijkman Institute for Molecular Biology, Addis Ababa University, Armauer Hansen Research Institute, Mahidol University, Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, Charles Darwin University, Menzies School of Health Research, Queen Elizabeth Hospital, Jiangsu Institute of Parasitic Diseases, Soochow University, Wellcome Sanger Institute, University of Oxford
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,350
Awards: G3497167089, Comparative incidence and clinical spectrum of Plasmodium knowlesi malaria, a longitudinal study in Sabah, Malaysia, Improving the treatment of Plasmodium vivax, Unraveling the molecular basis for vivax malaria's unhealthy attraction to human reticulocytes, G646906310, G6962367781, G7597818247, Improving the treatment of Plasmodium vivax, G8379199297
OpenAlex ID: W3041642436