Show simple item record

dc.contributor.authorOpi, DH
dc.contributor.authorBoyle, MJ
dc.contributor.authorMcLean, ARD
dc.contributor.authorReiling, L
dc.contributor.authorChan, JA
dc.contributor.authorStanisic, DI
dc.contributor.authorUra, A
dc.contributor.authorMueller, I
dc.contributor.authorFowkes, FJI
dc.contributor.authorRogerson, SJ
dc.contributor.authorBeeson, JG
dc.date.accessioned2021-09-07T01:19:19Z
dc.date.available2021-09-07T01:19:19Z
dc.date.issued2021
dc.identifier.issn1741-7015
dc.identifier.doi10.1186/s12916-021-02061-x
dc.identifier.urihttp://hdl.handle.net/10072/407690
dc.description.abstractBackground: The pathogenesis of malaria in pregnancy (MiP) involves accumulation of P. falciparum-infected red blood cells (pRBCs) in the placenta, contributing to poor pregnancy outcomes. Parasite accumulation is primarily mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1). Magnitude of IgG to pRBCs has been associated with reduced risk of MiP in some studies, but associations have been inconsistent. Further, antibody effector mechanisms are poorly understood, and the role of antibody complement interactions is unknown. Methods: Studying a longitudinal cohort of pregnant women (n=302) from a malaria-endemic province in Papua New Guinea (PNG), we measured the ability of antibodies to fix and activate complement using placental binding pRBCs and PfEMP1 recombinant domains. We determined antibody-mediated complement inhibition of pRBC binding to the placental receptor, chondroitin sulfate A (CSA), and associations with protection against placental parasitemia. Results: Some women acquired antibodies that effectively promoted complement fixation on placental-binding pRBCs. Complement fixation correlated with IgG1 and IgG3 antibodies, which dominated the response. There was, however, limited evidence for membrane attack complex activity or pRBC lysis or killing. Importantly, a higher magnitude of complement fixing antibodies was prospectively associated with reduced odds of placental infection at delivery. Using genetically modified P. falciparum and recombinant PfEMP1 domains, we found that complement-fixing antibodies primarily targeted a specific variant of PfEMP1 (known as VAR2CSA). Furthermore, complement enhanced the ability of antibodies to inhibit pRBC binding to CSA, which was primarily mediated by complement C1q protein. Conclusions: These findings provide new insights into mechanisms mediating immunity to MiP and reveal potential new strategies for developing malaria vaccines that harness antibody-complement interactions.
dc.description.peerreviewedYes
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.relation.ispartofpagefrom201
dc.relation.ispartofissue1
dc.relation.ispartofjournalBMC Medicine
dc.relation.ispartofvolume19
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchHealth sciences
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchcode3107
dc.subject.fieldofresearchcode42
dc.subject.fieldofresearchcode3204
dc.titleReduced risk of placental parasitemia associated with complement fixation on Plasmodium falciparum by antibodies among pregnant women
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationOpi, DH; Boyle, MJ; McLean, ARD; Reiling, L; Chan, JA; Stanisic, DI; Ura, A; Mueller, I; Fowkes, FJI; Rogerson, SJ; Beeson, JG, Reduced risk of placental parasitemia associated with complement fixation on Plasmodium falciparum by antibodies among pregnant women, BMC Medicine, 2021, 19 (1), pp. 201
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.date.updated2021-09-06T22:20:02Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
gro.hasfulltextFull Text
gro.griffith.authorStanisic, Danielle
gro.griffith.authorBoyle, Michelle


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record