IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBL beta 3_D4 domain, and peptides located within these constructs in children with cerebral malaria

Cyril Badaut (1) , Pimnitah Visitdesotrakul (2) , Aurelie Chabry (3) , Pascal Bigey (4) , Bernard Tornyigah (3) , Jocelyne Roman (3) , Jules Alao Maroufou (5) , Annick Amoussou (6) , Blaise Serge Ayivi (6) , Gratien Sagbo (6) , Nicaise Tuikue Ndam (3) , Andrew V. Oleinikov (2) , Rachida Tahar (3)

1 IRBA - Institut de Recherche Biomédicale des Armées [Antenne Marseille]
2 Florida Atlantic University [Boca Raton]
3 MERIT - UMR_D 261 - Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique
4 UTCBS - UM 4 (UMR 8258 / U1267) - Unité de Technologies Chimiques et Biologiques pour la Santé
5 CHU-MEL - Centre Hospitalier Universitaire de la Mère et de l'Enfant Lagune
6 CNHU-HKM - Centre National Hospitalier Universitaire Hubert K. Maga de Cotonou

The Plasmodium falciparum erythrocyte-membrane-protein-1 (PF3D7_1150400/PF11_0521) contains both domain cassette DC13 and DBL beta 3 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 DBL beta 3_D4 recombinant constructs, and five peptides located within these constructs, specifically in DBL alpha 1.7_D2 and DBL beta 3_D4 domains. We found significant IgG responses against the entire DC13, PF11_0521_DBL beta 3_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 DBL beta 3 B3-34 peptide that contains essential residues involved in the interaction between PF11_0521 DBL beta 3_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 DBL beta 3_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.

Mots clés: ERYTHROCYTE-MEMBRANE PROTEIN-1; NATURALLY ACQUIRED-IMMUNITY; BLOOD-STAGE ANTIGENS; PLASMODIUM-FALCIPARUM; INFECTED ERYTHROCYTES; ANTIBODIES; IDENTIFICATION; BINDING; PROTECTION; RECEPTOR

Domaines: Parasitologie

Cyril Badaut, Pimnitah Visitdesotrakul, Aurelie Chabry, Pascal Bigey, Bernard Tornyigah, et al.. IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBL beta 3_D4 domain, and peptides located within these constructs in children with cerebral malaria. Scientific Reports, 2021, 11 (1), ⟨10.1038/s41598-021-82444-5⟩. ⟨hal-03292042⟩