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dc.contributor.authorIrani, Vashti-
dc.contributor.authorRamsland, Paul A-
dc.contributor.authorGuy, Andrew J-
dc.contributor.authorSiba, Peter M-
dc.contributor.authorMueller, Ivo-
dc.contributor.authorRichards, Jack S-
dc.contributor.authorBeeson, James G-
dc.identifier.citationClinical Infectious Diseases 2016; 61(8): 1244-1252en_US
dc.description.abstractBACKGROUND: The targets and mechanisms of human immunity to malaria are poorly understood, which poses a major barrier to malaria vaccine development. Antibodies play a key role in human immunity and may act by inhibiting receptor-binding functions of key merozoite invasion ligands. Antibodies to the major invasion ligand and vaccine candidate, erythrocyte-binding antigen 175 (EBA-175), have been linked with protection, but how these antibodies function has not been established. METHODS: We developed 2 new assays that quantify the ability of antibodies to inhibit binding of EBA-175 to its erythrocyte receptor, glycophorin A, using either native or recombinant EBA-175. Binding-inhibitory antibodies were evaluated in a longitudinal cohort study of Papua New Guinean children and related to risk of malaria, age, infection status, and markers of parasite exposure. RESULTS: Binding-inhibition assays (BIAs) were reproducible, and the 2 assays had a high level of agreement. Inhibitory antibodies were common among children, acquired in association with markers of increasing parasite exposure, and high in those children with active infection. Inhibitory antibodies correlated with total immunoglobulin G levels to the EBA-175 binding domain (region II). Importantly, binding-inhibitory antibodies were significantly associated with protection from symptomatic malaria when measured using either BIA. CONCLUSIONS: Findings suggest that naturally acquired binding-inhibitory antibodies are an important functional mechanism that contributes to protection against malaria and further supports the potential of EBA-175 as a vaccine candidate. Identifying vaccines and approaches that induce potent binding-inhibitory antibodies may be a valuable strategy in the development of highly efficacious malaria vaccines.en_US
dc.subjectPlasmodium falciparumen_US
dc.subjectBinding inhibitionen_US
dc.titleAcquisition of functional antibodies that block the binding of erythrocyte-binding antigen 175 and protection against plasmodium falciparum malaria in childrenen_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleClinical Infectious Diseasesen_US
dc.identifier.affiliationAustin Health, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationCentre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Parkville, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Immunology, Monash University, Melbourne, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Surgery, Austin Health, University of Melbourne, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationSchool of Biomedical Sciences, Curtin Health Innovation Research Institute-Biosciences, Curtin University, Perth, Western Australia, Australiaen_US
dc.identifier.affiliationPapua New Guinea Institute of Medical Research, Goroka, Papua New Guineaen_US
dc.identifier.affiliationInfection and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australiaen_US
dc.identifier.affiliationBarcelona Centre for International Health Research, Barcelona, Spainen_US
dc.identifier.affiliationDepartment of Microbiology, Monash University, Clayton, Victoria, Australiaen_US
dc.type.austinJournal Articleen_US
item.fulltextNo Fulltext-
item.openairetypeJournal Article- (University of Melbourne)-
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