title: Identification and characterization of B-cell epitopes in the DBL4ε domain of VAR2CSA.
abstract: Malaria during pregnancy in Plasmodium falciparum endemic regions is a major cause of mortality and severe morbidity. VAR2CSA is the parasite ligand responsible for sequestration of Plasmodium falciparum infected erythrocytes to the receptor chondroitin sulfate A (CSA) in the placenta and is the leading candidate for a placental malaria vaccine. Antibodies induced in rats against the recombinant DBL4ε domain of VAR2CSA inhibit the binding of a number of laboratory and field parasite isolates to CSA. In this study, we used a DBL4ε peptide-array to identify epitopes targeted by DBL4ε-specific antibodies that inhibit CSA-binding of infected erythrocytes. We identified three regions of overlapping peptides which were highly antigenic. One peptide region distinguished itself particularly by showing a clear difference in the binding profile of highly parasite blocking IgG compared to the IgG with low capacity to inhibit parasite adhesion to CSA. This region was further characterized and together these results suggest that even though antibodies against the synthetic peptides which cover this region did not recognize native protein, the results using the mutant domain suggest that this linear epitope might be involved in the induction of inhibitory antibodies induced by the recombinant DBL4ε domain.
authors.affiliation: Centre for Medical Parasitology at the Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sisse B
authors.initials: SB
authors.lastname: Ditlev
authors.forename: Morten A
authors.initials: MA
authors.lastname: Nielsen
authors.forename: Mafalda
authors.initials: M
authors.lastname: Resende
authors.forename: Mette Ø
authors.initials: MØ
authors.lastname: Agerbæk
authors.forename: Vera V
authors.initials: VV
authors.lastname: Pinto
authors.forename: Pernille H
authors.initials: PH
authors.lastname: Andersen
authors.forename: Pamela
authors.initials: P
authors.lastname: Magistrado
authors.forename: John
authors.initials: J
authors.lastname: Lusingu
authors.forename: Madeleine
authors.initials: M
authors.lastname: Dahlbäck
authors.forename: Thor G
authors.initials: TG
authors.lastname: Theander
authors.forename: Ali
authors.initials: A
authors.lastname: Salanti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000737:chemistry / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000276:immunology; D002448:Cell Adhesion; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D016014:Linear Models; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D050505:Mutant Proteins / Q000737:chemistry / Q000276:immunology; D010271:Parasites / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010963:Plasmodium falciparum / Q000166:cytology / Q000276:immunology; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D051381:Rats; D016415:Sequence Alignment
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018985:Epitopes, B-Lymphocyte; D007106:Immune Sera; D050505:Mutant Proteins; D010455:Peptides; C512601:VAR2CSA protein, Plasmodium falciparum