title: Opsonising antibodies to P. falciparum merozoites associated with immunity to clinical malaria.
abstract: Naturally acquired humoral immunity to the malarial parasite Plasmodium falciparum can protect against disease, although the precise mechanisms remain unclear. Although antibody levels can be measured by ELISA, few studies have investigated functional antibody assays in relation to clinical outcomes. In this study we applied a recently developed functional assay of antibody-mediated opsonisation of merozoites, to plasma samples from a longitudinal cohort study conducted in a malaria endemic region of Papua New Guinea (PNG). Phagocytic activity was quantified by flow cytometry using a standardized and high-throughput protocol, and was subsequently evaluated for association with protection from clinical malaria and high-density parasitemia. Opsonising antibody responses were found to: i) increase with age, ii) be enhanced by concurrent infection, and iii) correlate with protection from clinical episodes and high-density parasitemia. Stronger protective associations were observed in individuals with no detectable parasitemia at baseline. This study presents the first evidence for merozoite phagocytosis as a correlate of acquired immunity and clinical protection against P. falciparum malaria.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia ; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Danika L
authors.initials: DL
authors.lastname: Hill
authors.forename: Emily M
authors.initials: EM
authors.lastname: Eriksson
authors.forename: Connie S N
authors.initials: CS
authors.lastname: Li Wai Suen
authors.forename: Chris Y
authors.initials: CY
authors.lastname: Chiu
authors.forename: Victoria
authors.initials: V
authors.lastname: Ryg-Cornejo
authors.forename: Leanne J
authors.initials: LJ
authors.lastname: Robinson
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siba
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.forename: Diana S
authors.initials: DS
authors.lastname: Hansen
authors.forename: Louis
authors.initials: L
authors.lastname: Schofield
mesh_terms: D000293:Adolescent; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D006801:Humans; D056724:Immunity, Humoral; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology*; D009000:Monocytes / Q000469:parasitology; D009895:Opsonin Proteins / Q000276:immunology*; D010219:Papua New Guinea; D018512:Parasitemia / Q000097:blood / Q000276:immunology; D010587:Phagocytosis; D010963:Plasmodium falciparum / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D009895:Opsonin Proteins
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