Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Natural and Vaccine-Induced Acquisition of Cross-Reactive IgG-Inhibiting ICAM-1-Specific Binding of a Plasmodium falciparum PfEMP1 Subtype Associated Specifically with Cerebral Malaria

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Reliable cell and tissue morphology-based diagnosis of endemic Burkitt lymphoma in resource-constrained settings in Ghana

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Meta-analysis of Plasmodium falciparum var Signatures Contributing to Severe Malaria in African Children and Indian Adults

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Cerebral malaria (CM) is a potentially deadly outcome of Plasmodium falciparum malaria that is precipitated by sequestration of infected erythrocytes (IEs) in the brain. The adhesion of IEs to brain endothelial cells is mediated by a subtype of parasite-encoded erythrocyte membrane protein 1 (PfEMP1) that facilitates dual binding to host intercellular adhesion molecule 1 (ICAM-1) and endothelial protein receptor C (EPCR). The PfEMP1 subtype is characterized by the presence of a particular motif (DBLβ_motif) in the constituent ICAM-1-binding DBLβ domain. The rate of natural acquisition of DBLβ_motif-specific IgG antibodies and the ability to induce such antibodies by vaccination are unknown, and the aim of this study was to provide such data. We used an enzyme-linked immunosorbent assay (ELISA) to measure DBLβ-specific IgG in plasma from Ghanaian children with malaria. The ability of human immune plasma and DBLβ-specific rat antisera to inhibit the interaction between ICAM-1 and DBLβ was assessed using ELISA and in vitro assays of IE adhesion under flow. The acquisition of DBLβ_motif-specific IgG coincided with age-specific susceptibility to CM. Broadly cross-reactive antibodies inhibiting the interaction between ICAM-1 and DBLβ_motif domains were detectable in immune plasma and in sera of rats immunized with specific DBLβ_motif antigens. Importantly, antibodies against the DBLβ_motif inhibited ICAM-1-specific in vitro adhesion of erythrocytes infected by four of five P. falciparum isolates from cerebral malaria patients. We conclude that natural exposure to P. falciparum as well as immunization with specific DBLβ_motif antigens can induce cross-reactive antibodies that inhibit the interaction between ICAM-1 and a broad range of DBLβ_motif domains. These findings raise hope that a vaccine designed specifically to prevent CM is feasible.

Original languageEnglish
JournalInfection and Immunity
Volume86
Issue number4
Pages (from-to) e00622-17
ISSN0019-9567
DOIs
Publication statusPublished - Apr 2018

    Research areas

  • Adolescent, Amino Acid Motifs, Antibodies, Neutralizing/immunology, Antibodies, Protozoan/immunology, Antigens, Protozoan/immunology, Binding Sites, Child, Child, Preschool, Cross Reactions/immunology, Ghana, Humans, Immunoglobulin G/immunology, Infant, Intercellular Adhesion Molecule-1/metabolism, Malaria Vaccines/immunology, Malaria, Cerebral/immunology, Malaria, Falciparum/immunology, Plasmodium falciparum/immunology, Protein Binding/immunology, Protein Interaction Domains and Motifs, Protozoan Proteins/chemistry, Tanzania

ID: 56396140