title: A plasma survey using 38 PfEMP1 domains reveals frequent recognition of the Plasmodium falciparum antigen VAR2CSA among young Tanzanian children.
abstract: PfEMP1 proteins comprise a family of variant antigens that appear on the surface of P. falciparum-infected erythrocytes and bind to multiple host receptors. Using a mammalian expression system and BioPlex technology, we developed an array of 24 protein constructs representing 38 PfEMP1 domains for high throughput analyses of receptor binding as well as total and functional antibody responses. We analyzed the reactivity of 561 plasma samples from 378 young Tanzanian children followed up to maximum 192 weeks of life in a longitudinal birth cohort. Surprisingly, reactivity to the DBL5 domain of VAR2CSA, a pregnancy malaria vaccine candidate, was most common, and the prevalence of reactivity was stable throughout early childhood. Reactivity to all other PfEMP1 constructs increased with age. Antibodies to the DBL2βC2(PF11_0521) domain, measured as plasma reactivity or plasma inhibition of ICAM1 binding, predicted reduced risk of hospitalization for severe or moderately severe malaria. These data suggest a role for VAR2CSA in childhood malaria and implicate DBL2βC2(PF11_0521) in protective immunity.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, United States of America. andrew.oleinikov@seattlebiomed.org
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Oleinikov
authors.forename: Valentina V
authors.initials: VV
authors.lastname: Voronkova
authors.forename: Isaac Tyler
authors.initials: IT
authors.lastname: Frye
authors.forename: Emily
authors.initials: E
authors.lastname: Amos
authors.forename: Robert
authors.initials: R
authors.lastname: Morrison
authors.forename: Michal
authors.initials: M
authors.lastname: Fried
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Duffy
mesh_terms: D000953:Antigens, Protozoan / Q000276:immunology*; D018955:CD36 Antigens / Q000378:metabolism; D003625:Data Collection; D005260:Female; D006760:Hospitalization; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000097:blood / Q000453:epidemiology / Q000628:therapy; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000097:blood* / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D012306:Risk; D013636:Tanzania / Q000453:epidemiology
chemical_list: D000953:Antigens, Protozoan; D018955:CD36 Antigens; D007074:Immunoglobulin G; D015800:Protozoan Proteins; C512601:VAR2CSA protein, Plasmodium falciparum; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D018799:Intercellular Adhesion Molecule-1