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<p>The frequently fatal outcome of cerebral malaria has been linked to the adhesion and accumulation in the cerebral microvasculature of infected erythrocytes (IEs), which express a particular type of <i>Plasmodium falciparum</i> erythrocyte membrane protein 1 (PfEMP1). This type, found in the A and B/A subsets of PfEMP1, contains a particular structural motif (DBLβ<sub>motif</sub>) and has dual affinity for the host vascular receptors ICAM-1 and EPCR. Here, we report the functional characterization of a mouse monoclonal antibody, mAb02, raised against eight different DBLβ<sub>motif</sub> domains. The antibody selectively recognizes DBLβ<sub>motif</sub>-positive PfEMP1 proteins and inhibits their binding to ICAM-1. It also recognizes IEs expressing DBLβ<sub>motif</sub>-positive PfEMP1 proteins on their surface and inhibits their adhesion to ICAM-1. The mAb02 epitope is located in an unfolded linker region of the ICAM-1-binding site of DBLβ<sub>motif</sub> and includes residues directly involved in the interaction between DBLβ<sub>motif</sub> and ICAM-1, as well as residues that are important for the positioning of the interacting residues. Our study shows that mAb02 targets a broadly conserved epitope that is found in PfEMP1 proteins binding to ICAM-1 and EPCR and implicated in the pathogenesis of cerebral malaria (CM). This suggests the potential of mAb02 in the development of monoclonal antibody-based intervention against CM and for identification of IEs with capacity to causing CM.</p>

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A monoclonal antibody selectively recognizing PfEMP1 proteins associated with cerebral malaria

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月6日

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  • Nanna Dalgaard,
  • Rebecca W. Olsen,
  • Yvonne Adams,
  • Blanca L. Mendez,
  • Jonas J. Rudbaek,
  • Sofie Amalie G. Bisholm,
  • Azizath Mousiliou,
  • Melanie R. Walker,
  • Lars Hviid,
  • Rachida Tahar,
  • Nicaise T. Ndam,
  • Lea Barfod,
  • Anja R. Jensen

摘要

The frequently fatal outcome of cerebral malaria has been linked to the adhesion and accumulation in the cerebral microvasculature of infected erythrocytes (IEs), which express a particular type of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). This type, found in the A and B/A subsets of PfEMP1, contains a particular structural motif (DBLβmotif) and has dual affinity for the host vascular receptors ICAM-1 and EPCR. Here, we report the functional characterization of a mouse monoclonal antibody, mAb02, raised against eight different DBLβmotif domains. The antibody selectively recognizes DBLβmotif-positive PfEMP1 proteins and inhibits their binding to ICAM-1. It also recognizes IEs expressing DBLβmotif-positive PfEMP1 proteins on their surface and inhibits their adhesion to ICAM-1. The mAb02 epitope is located in an unfolded linker region of the ICAM-1-binding site of DBLβmotif and includes residues directly involved in the interaction between DBLβmotif and ICAM-1, as well as residues that are important for the positioning of the interacting residues. Our study shows that mAb02 targets a broadly conserved epitope that is found in PfEMP1 proteins binding to ICAM-1 and EPCR and implicated in the pathogenesis of cerebral malaria (CM). This suggests the potential of mAb02 in the development of monoclonal antibody-based intervention against CM and for identification of IEs with capacity to causing CM.