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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-82444-5 |
| _version_ | 1818424910511341568 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T14:05:33Z |
| format | Article |
| id | doaj.art-6e152901015e4606ac4807d0bf59441a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T14:05:33Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6e152901015e4606ac4807d0bf59441a2022-12-21T22:58:34ZengNature PortfolioScientific Reports2045-23222021-02-0111111210.1038/s41598-021-82444-5IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malariaBadaut Cyril0Pimnitah Visitdesotrakul1Aurélie Chabry2Pascal Bigey3Bernard Tornyigah4Jocelyne Roman5Jules Alao Maroufou6Annick Amoussou7Blaise Serge Ayivi8Gratien Sagbo9Nicaise Tuikue Ndam10Andrew V. Oleinikov11Rachida Tahar12Institut de Recherche Biomédicale des Armées, National Reference Laboratory for ArbovirusesCharles E. Schmidt College of Medicine, Florida Atlantic UniversityUniversité de Paris, MERIT, IRDUniversité de Paris, UMR 8151 CNRS - INSERM U1022 - ENSCPUniversité de Paris, MERIT, IRDUniversité de Paris, MERIT, IRDDépartement de Pédiatrie, Hôpital Mère-Enfant La Lagune (CHUMEL) CotonouService de Pédiatrie, Centre Hospitalo-Universitaire, Suruléré (CHU-SuruléréService de Pédiatrie, Centre National Hospitalo-Universitaire (CNHU)Service de Pédiatrie, Centre National Hospitalo-Universitaire (CNHU)Université de Paris, MERIT, IRDCharles E. Schmidt College of Medicine, Florida Atlantic UniversityUniversité de Paris, MERIT, IRDAbstract 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.https://doi.org/10.1038/s41598-021-82444-5 |
| spellingShingle | 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 Scientific Reports |
| 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_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_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_sort | igg acquisition against pfemp1 pf11 0521 domain cassette dc13 dblβ3 d4 domain and peptides located within these constructs in children with cerebral malaria |
| url | https://doi.org/10.1038/s41598-021-82444-5 |
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