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dc.contributor.authorL. King, Christopher
dc.contributor.authorMichon, Pascal
dc.contributor.authorShakri, Ahmad Rushdi
dc.contributor.authorMarcotty, Alexandra
dc.contributor.authorStanisic, Danielle
dc.contributor.authorA. Zimmerman, Peter
dc.contributor.authorL. Cole-Tobian, Jennifer
dc.contributor.authorMueller, Ivo
dc.contributor.authorE. Chitnis, Chetan
dc.date.accessioned2017-05-03T16:01:46Z
dc.date.available2017-05-03T16:01:46Z
dc.date.issued2008
dc.date.modified2013-06-04T03:49:03Z
dc.identifier.issn10916490
dc.identifier.doi10.1073/pnas.0800371105
dc.identifier.urihttp://hdl.handle.net/10072/48163
dc.description.abstractIndividuals residing in malaria-endemic regions acquire protective immunity after repeated infection with malaria parasites; however, mechanisms of protective immunity and their immune correlates are poorly understood. Blood-stage infection with Plasmodium vivax depends completely on interaction of P. vivax Duffy-binding protein (PvDBP) with the Duffy antigen on host erythrocytes. Here, we performed a prospective cohort treatment/reinfection study of children (5-14 years) residing in a P. vivax-endemic region of Papua New Guinea (PNG) in which children were cleared of blood-stage infection and then examined biweekly for reinfection for 25 weeks. To test the hypothesis that naturally acquired binding inhibitory antibodies (BIAbs) targeting PvDBP region II (PvDBPII) provide protection against P. vivax infection, we used a quantitative receptor-binding assay to distinguish between antibodies that merely recognize PvDBP and those that inhibit binding to Duffy. The presence of high-level BIAbs (>90% inhibition of PvDBPII-Duffy binding, n = 18) before treatment was associated with delayed time to P. vivax reinfection diagnosed by light microscopy (P = 0.02), 55% reduced risk of P. vivax reinfection (Hazard's ratio = 0.45, P = 0.04), and 48% reduction in geometric mean P. vivax parasitemia (P < 0.001) when compared with children with low-level BIAbs (n = 148). Further, we found that stable, high-level BIAbs displayed strain-transcending inhibition by reducing reinfection with similar efficiency of PNG P. vivax strains characterized by six diverse PvDBPII haplotypes. These observations demonstrate a functional correlate of protective immunity in vivo and provide support for developing a vaccine against P. vivax malaria based on PvDBPII.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNational Academy of Sciences
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom8363
dc.relation.ispartofpageto8368
dc.relation.ispartofissue24
dc.relation.ispartofjournalProceedings of the National Academy of Sciences of the United States of America
dc.relation.ispartofvolume105
dc.rights.retentionY
dc.subject.fieldofresearchMedical and Health Sciences not elsewhere classified
dc.subject.fieldofresearchcode119999
dc.titleNaturally acquired Duffy-binding protein-specific binding inhibitory antibodies confer protection from blood-stage Plasmodium vivax infection
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2008
gro.hasfulltextNo Full Text
gro.griffith.authorStanisic, Danielle


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