title: Limited cross-reactivity among domains of the Plasmodium falciparum clone 3D7 erythrocyte membrane protein 1 family.
abstract: The var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family is responsible for antigenic variation and sequestration of infected erythrocytes during malaria. We have previously grouped the 60 PfEMP1 variants of P. falciparum clone 3D7 into groups A and B/A (category A) and groups B, B/C, and C (category non-A). Expression of category A molecules is associated with severe malaria, and that of category non-A molecules is associated with uncomplicated malaria and asymptomatic infection. Here we assessed cross-reactivity among 60 different recombinant PfEMP1 domains derived from clone 3D7 by using a competition enzyme-linked immunosorbent assay and a pool of plasma from 63 malaria-exposed Tanzanian individuals. We conclude that naturally acquired antibodies are largely directed toward epitopes varying between different domains with a few, mainly category A, domains sharing cross-reactive antibody epitopes. Identification of groups of serological cross-reacting molecules is pivotal for the development of vaccines based on PfEMP1.
authors.affiliation: University of Copenhagen, Department of Medical Microbiology and Immunology, Panum 24.2.24, Blegdamsvej 3, Copenhagen DK-2200, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Joergensen
authors.forename: Louise
authors.initials: L
authors.lastname: Turner
authors.forename: Pamela
authors.initials: P
authors.lastname: Magistrado
authors.forename: Madeleine A
authors.initials: MA
authors.lastname: Dahlbäck
authors.forename: Lasse S
authors.initials: LS
authors.lastname: Vestergaard
authors.forename: John P
authors.initials: JP
authors.lastname: Lusingu
authors.forename: Martha
authors.initials: M
authors.lastname: Lemnge
authors.forename: Ali
authors.initials: A
authors.lastname: Salanti
authors.forename: Thor G
authors.initials: TG
authors.lastname: Theander
authors.forename: Anja T R
authors.initials: AT
authors.lastname: Jensen
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001667:Binding, Competitive; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D016056:Immunodominant Epitopes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum