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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

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@article{3856279dd04e4a499d8322e757300d18,
title = "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",
abstract = "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.",
keywords = "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",
author = "Olsen, {Rebecca W} and Gertrude Ecklu-Mensah and Anja Bengtsson and Ofori, {Michael F} and Lusingu, {John P A} and Castberg, {Filip C} and Lars Hviid and Yvonne Adams and Jensen, {Anja T R}",
note = "Copyright {\circledC} 2018 Olsen et al.",
year = "2018",
month = "4",
doi = "10.1128/IAI.00622-17",
language = "English",
volume = "86",
pages = "e00622--17",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "4",

}

RIS

TY - JOUR

T1 - 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

AU - Olsen, Rebecca W

AU - Ecklu-Mensah, Gertrude

AU - Bengtsson, Anja

AU - Ofori, Michael F

AU - Lusingu, John P A

AU - Castberg, Filip C

AU - Hviid, Lars

AU - Adams, Yvonne

AU - Jensen, Anja T R

N1 - Copyright © 2018 Olsen et al.

PY - 2018/4

Y1 - 2018/4

N2 - 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.

AB - 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.

KW - Adolescent

KW - Amino Acid Motifs

KW - Antibodies, Neutralizing/immunology

KW - Antibodies, Protozoan/immunology

KW - Antigens, Protozoan/immunology

KW - Binding Sites

KW - Child

KW - Child, Preschool

KW - Cross Reactions/immunology

KW - Ghana

KW - Humans

KW - Immunoglobulin G/immunology

KW - Infant

KW - Intercellular Adhesion Molecule-1/metabolism

KW - Malaria Vaccines/immunology

KW - Malaria, Cerebral/immunology

KW - Malaria, Falciparum/immunology

KW - Plasmodium falciparum/immunology

KW - Protein Binding/immunology

KW - Protein Interaction Domains and Motifs

KW - Protozoan Proteins/chemistry

KW - Tanzania

U2 - 10.1128/IAI.00622-17

DO - 10.1128/IAI.00622-17

M3 - Journal article

VL - 86

SP - e00622-17

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 4

ER -

ID: 56396140