ArticlePLoS pathogens2009
High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 69 citations in OpenAlex.
- Breaking the bind: PfEMP1-specific antibodies in cerebral malaria.Frontiers in immunology · 2025Review
- Profiling the Plasmodium falciparum Erythrocyte Membrane Protein 1-Specific Immununoglobulin G Response Among Ghanaian Children With Hemoglobin S and C.The Journal of infectious diseases · 2024Article
- Antibody to Plasmodium falciparum Variant Surface Antigens, var Gene Transcription, and ABO Blood Group in Children With Severe or Uncomplicated Malaria.The Journal of infectious diseases · 2023Article
- High-Throughput Antibody Profiling Identifies Targets of Protective Immunity againstBiomolecules · 2023Article
- Knobs, Adhesion, and Severe Falciparum Malaria.Tropical medicine and infectious disease · 2023Review
- ICAM-1-binding Plasmodium falciparum erythrocyte membrane protein 1 variants elicits opsonic-phagocytosis IgG responses in Beninese children.Scientific reports · 2022Article
- An Invariant Protein That Colocalizes With VAR2CSA on Plasmodium falciparum-Infected Red Cells Binds to Chondroitin Sulfate A.The Journal of infectious diseases · 2022Article
- Antibody-Dependent THP-1 Cell-Mediated Phagocytosis of Plasmodium falciparum-Infected Erythrocytes.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Malaria Parasite Plasmodium falciparum Proteins on the Surface of Infected Erythrocytes as Targets for Novel Drug Discovery.Biochemistry. Biokhimiia · 2022Review
- Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding betweenInternational journal of molecular sciences · 2021Article
- 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 · 2021Article
- PfEMP1 A-Type ICAM-1-Binding Domains Are Not Associated with Cerebral Malaria in Beninese Children.mBio · 2020Article
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- Stringent Selection of KnobbyMicroorganisms · 2020Article
- Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it.Immunological reviews · 2020Review
- Structural insights into diverse modes of ICAM-1 binding byProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Comprehensive analysis of Fc-mediated IgM binding to the Plasmodium falciparum erythrocyte membrane protein 1 family in three parasite clones.Scientific reports · 2019Article
- The impact of early life exposure to Plasmodium falciparum on the development of naturally acquired immunity to malaria in young Malawian children.Malaria journal · 2019Article
- Plasmodium falciparum infected erythrocytes can bind to host receptors integrins αVβ3 and αVβ6 through DBLδ1_D4 domain of PFL2665c PfEMP1 protein.Scientific reports · 2018Article
- Antibodies to Intercellular Adhesion Molecule 1-Binding Plasmodium falciparum Erythrocyte Membrane Protein 1-DBLβ Are Biomarkers of Protective Immunity to Malaria in a Cohort of Young Children from Papua New Guinea.Infection and immunity · 2018Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Plasmodium falciparum-infected erythrocytes bind endothelial receptors to sequester in vascular beds, and binding to ICAM1 has been implicated in cerebral malaria. Binding to ICAM1 may be mediated by the variant surface antigen family PfEMP1: for example, 6 of 21 DBLbetaC2 domains from the IT4 strain PfEMP1 repertoire were shown to bind ICAM1, and the PfEMP1 containing these 6 domains are all classified as Group B or C type. In this study, we surveyed binding of ICAM1 to 16 DBLbetaC2 domains of the 3D7 strain PfEMP1 repertoire, using a high throughput Bioplex assay format. Only one DBL2betaC2 domain from the Group A PfEMP1 PF11_0521 showed strong specific binding. Among these 16 domains, DBL2betaC2(PF11_0521) best preserved the residues previously identified as conserved in ICAM1-binding versus non-binding domains. Our analyses further highlighted the potential role of conserved residues within predominantly non-conserved flexible loops in adhesion, and, therefore, as targets for intervention. Our studies also suggest that the structural/functional DBLbetaC2 domain involved in ICAM1 binding includes about 80 amino acid residues upstream of the previously suggested DBLbetaC2 domain. DBL2betaC2(PF11_0521) binding to ICAM1 was inhibited by immune sera from east Africa but not by control US sera. Neutralizing antibodies were uncommon in children but common in immune adults from east Africa. Inhibition of binding was much more efficient than reversal of binding, indicating a strong interaction between DBL2betaC2(PF11_0521) and ICAM1. Our high throughput approach will significantly accelerate studies of PfEMP1 binding domains and protective antibody responses.
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