IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria

Abstract The Plasmodium falciparum erythrocyte-membrane-protein-1 (PF3D7_1150400/PF11_0521) contains both domain cassette DC13 and DBLβ3 domain binding to EPCR and ICAM-1 receptors, respectively. This type of PfEMP1 proteins with dual binding specificity mediate specific interactions with brain micr...

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Autores principales: Badaut Cyril, Pimnitah Visitdesotrakul, Aurélie Chabry, Pascal Bigey, Bernard Tornyigah, Jocelyne Roman, Jules Alao Maroufou, Annick Amoussou, Blaise Serge Ayivi, Gratien Sagbo, Nicaise Tuikue Ndam, Andrew V. Oleinikov, Rachida Tahar
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:6e152901015e4606ac4807d0bf59441a2021-12-02T14:27:02ZIgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria10.1038/s41598-021-82444-52045-2322https://doaj.org/article/6e152901015e4606ac4807d0bf59441a2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82444-5https://doaj.org/toc/2045-2322Abstract The Plasmodium falciparum erythrocyte-membrane-protein-1 (PF3D7_1150400/PF11_0521) contains both domain cassette DC13 and DBLβ3 domain binding to EPCR and ICAM-1 receptors, respectively. This type of PfEMP1 proteins with dual binding specificity mediate specific interactions with brain micro-vessels endothelium leading to the development of cerebral malaria (CM). Using plasma collected from children at time of hospital admission and after 30 days, we study an acquisition of IgG response to PF3D7_1150400/PF11_0521 DC13 and DBLβ3_D4 recombinant constructs, and five peptides located within these constructs, specifically in DBLα1.7_D2 and DBLβ3_D4 domains. We found significant IgG responses against the entire DC13, PF11_0521_DBLβ3_D4 domain, and peptides. The responses varied against different peptides and depended on the clinical status of children. The response was stronger at day 30, and mostly did not differ between CM and uncomplicated malaria (UM) groups. Specifically, the DBLβ3 B3-34 peptide that contains essential residues involved in the interaction between PF11_0521 DBLβ3_D4 domain and ICAM-1 receptor demonstrated significant increase in reactivity to IgG1 and IgG3 antibodies at convalescence. Further, IgG reactivity in CM group at time of admission against functionally active (ICAM-1-binding) PF11_0521 DBLβ3_D4 domain was associated with protection against severe anemia. These results support development of vaccine based on the PF3D7_1150400/PF11_0521 structures to prevent CM.Badaut CyrilPimnitah VisitdesotrakulAurélie ChabryPascal BigeyBernard TornyigahJocelyne RomanJules Alao MaroufouAnnick AmoussouBlaise Serge AyiviGratien SagboNicaise Tuikue NdamAndrew V. OleinikovRachida TaharNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Badaut Cyril
Pimnitah Visitdesotrakul
Aurélie Chabry
Pascal Bigey
Bernard Tornyigah
Jocelyne Roman
Jules Alao Maroufou
Annick Amoussou
Blaise Serge Ayivi
Gratien Sagbo
Nicaise Tuikue Ndam
Andrew V. Oleinikov
Rachida Tahar
IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria
description Abstract The Plasmodium falciparum erythrocyte-membrane-protein-1 (PF3D7_1150400/PF11_0521) contains both domain cassette DC13 and DBLβ3 domain binding to EPCR and ICAM-1 receptors, respectively. This type of PfEMP1 proteins with dual binding specificity mediate specific interactions with brain micro-vessels endothelium leading to the development of cerebral malaria (CM). Using plasma collected from children at time of hospital admission and after 30 days, we study an acquisition of IgG response to PF3D7_1150400/PF11_0521 DC13 and DBLβ3_D4 recombinant constructs, and five peptides located within these constructs, specifically in DBLα1.7_D2 and DBLβ3_D4 domains. We found significant IgG responses against the entire DC13, PF11_0521_DBLβ3_D4 domain, and peptides. The responses varied against different peptides and depended on the clinical status of children. The response was stronger at day 30, and mostly did not differ between CM and uncomplicated malaria (UM) groups. Specifically, the DBLβ3 B3-34 peptide that contains essential residues involved in the interaction between PF11_0521 DBLβ3_D4 domain and ICAM-1 receptor demonstrated significant increase in reactivity to IgG1 and IgG3 antibodies at convalescence. Further, IgG reactivity in CM group at time of admission against functionally active (ICAM-1-binding) PF11_0521 DBLβ3_D4 domain was associated with protection against severe anemia. These results support development of vaccine based on the PF3D7_1150400/PF11_0521 structures to prevent CM.
format article
author Badaut Cyril
Pimnitah Visitdesotrakul
Aurélie Chabry
Pascal Bigey
Bernard Tornyigah
Jocelyne Roman
Jules Alao Maroufou
Annick Amoussou
Blaise Serge Ayivi
Gratien Sagbo
Nicaise Tuikue Ndam
Andrew V. Oleinikov
Rachida Tahar
author_facet Badaut Cyril
Pimnitah Visitdesotrakul
Aurélie Chabry
Pascal Bigey
Bernard Tornyigah
Jocelyne Roman
Jules Alao Maroufou
Annick Amoussou
Blaise Serge Ayivi
Gratien Sagbo
Nicaise Tuikue Ndam
Andrew V. Oleinikov
Rachida Tahar
author_sort Badaut Cyril
title IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria
title_short IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria
title_full IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria
title_fullStr IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria
title_full_unstemmed IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria
title_sort igg acquisition against pfemp1 pf11_0521 domain cassette dc13, dblβ3_d4 domain, and peptides located within these constructs in children with cerebral malaria
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/6e152901015e4606ac4807d0bf59441a
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