{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:53:40Z","timestamp":1782370420745,"version":"3.54.5"},"reference-count":133,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Antibodies against\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    erythrocyte membrane protein 1 (PfEMP1) on infected erythrocytes (IEs) play a central role in naturally acquired protection against cerebral malaria (CM), yet the determinants of effective humoral immunity remain incompletely defined. We review evidence from seroepidemiological, functional, and mechanistic studies demonstrating that antibodies to endothelial protein C receptor (EPCR)\u2010binding cysteine-rich interdomain regions (CIDR)\u03b11 and Duffy binding-like (DBL)\u03b2 domains associated with dual EPCR and intercellular adhesion molecule 1 (ICAM1) binding correlate with reduced risk of CM, while responses to rosetting\u2010associated domains (DBL\u03b1, CIDR\u03b3) and other domains are less well characterized. We synthesize findings on antibody kinetics\u2014early, durable responses to Group A variants versus delayed, transient responses to Groups B and C\u2014and on effector mechanisms including opsonic phagocytosis, complement activation, and Fc glycosylation. We highlight methodological challenges in measuring PfEMP1\u2010specific immunity, such as antigenic switching, differences between assays using single domains and native protein on IEs, and the need for physiologically relevant 3D vascular models. Finally, we identify key research priorities: mapping immunodominant epitopes across variant repertoires; longitudinal cohort studies to track antibody maturation and post\u2010translational modifications; and the development of broadly inhibitory monoclonal antibodies. Addressing these gaps will be critical for designing vaccines and therapeutics that harness protective antibody functions to prevent CM.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1681852","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:23:09Z","timestamp":1761805389000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Breaking the bind: PfEMP1-specific antibodies in cerebral malaria"],"prefix":"10.3389","volume":"16","author":[{"given":"Josephine P.","family":"Banda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isobel S.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonney","family":"Nyirenda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth H.","family":"Aitken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Rogerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"B1","volume-title":"World Malaria Report 2024","year":"2024"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/9781118493816.ch1","article-title":"Introduction","author":"Chauhan","year":"2016","journal-title":"Recent Adv Malaria Advances in Malaria Research"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nm986","article-title":"Differentiating the pathologies of cerebral malaria by postmortem parasite counts","volume":"10","author":"Taylor","year":"2004","journal-title":"Nat Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/nature01097","article-title":"Genome sequence of the human malaria parasite Plasmodium falciparum","volume":"419","author":"Gardner","year":"2002","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e1000933","DOI":"10.1371\/journal.pcbi.1000933","article-title":"Plasmodium falciparum erythrocyte membrane protein 1 diversity in seven genomes \u2013 divide and conquer","volume":"6","author":"Rask","year":"2010","journal-title":"PloS Comput Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12183","article-title":"Malaria\u2019s deadly grip: Cytoadhesion of Plasmodium falciparum-infected erythrocytes","volume":"15","author":"Smith","year":"2013","journal-title":"Cell Microbiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/0092-8674(95)900543","article-title":"Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes","volume":"82","author":"Baruch","year":"1995","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s0166-6851(00)00279-6","article-title":"Classification of adhesive domains in the Plasmodium falciparum Erythrocyte Membrane Protein 1 family","volume":"110","author":"Smith","year":"2000","journal-title":"Mol Biochem Parasitol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e1000386","DOI":"10.1371\/journal.ppat.1000386","article-title":"High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies","volume":"5","author":"Oleinikov","year":"2009","journal-title":"PloS Pathog"},{"key":"B10","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1111\/j.1365-2958.2007.06019","article-title":"Mapping a common interaction site used by Plasmodium falciparum Duffy binding-like domains to bind diverse host receptors","volume":"67","author":"Howell","year":"2008","journal-title":"Mol Microbiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12837","article-title":"The structural basis for CD36 binding by the malaria parasite","volume":"7","author":"Hsieh","year":"2016","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/415673a","article-title":"The pathogenic basis of malaria","volume":"415","author":"Miller","year":"2002","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045658","article-title":"The Density of Knobs on Plasmodium falciparum-Infected Erythrocytes Depends on Developmental Age and Varies among Isolates","volume":"7","author":"Quadt","year":"2012","journal-title":"PloS One"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv205","article-title":"Quantitative assessment of multiorgan sequestration of parasites in fatal pediatric cerebral malaria","volume":"212","author":"Milner","year":"2015","journal-title":"J Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/nyas.12690","article-title":"The pathogenesis of pediatric cerebral malaria: eye exams, autopsies, and neuroimaging","volume":"1342","author":"Taylor","year":"2015","journal-title":"Ann N Y Acad Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2006.75.790","article-title":"Malarial retinopathy: a newly established diagnostic sign in severe malaria","volume":"75","author":"Beare","year":"2006","journal-title":"Am J Trop Med Hyg"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12807","article-title":"Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it","volume":"293","author":"Jensen","year":"2020","journal-title":"Immunol Rev"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12521","article-title":"Malaria-derived hemozoin exerts early modulatory effects on the phenotype and maturation of human dendritic cells","volume":"18","author":"Bujila","year":"2016","journal-title":"Cell Microbiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4172\/2329-891X.1000126","article-title":"Toll-like receptors and malaria \u2013 sensing and susceptibility","volume":"2","author":"Eriksson","year":"2013","journal-title":"J Trop Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00324","article-title":"Cytokines and chemokines in cerebral malaria pathogenesis","volume":"7","author":"Dunst","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e1001021","DOI":"10.1371\/journal.ppat.1001021","article-title":"Plasmodium falciparum adhesion on human brain microvascular endothelial cells involves transmigration-like cup formation and induces opening of intercellular junctions","volume":"6","author":"Jambou","year":"2010","journal-title":"PloS Pathog"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI133474","article-title":"CD8+ T cells target cerebrovasculature in children with cerebral malaria","volume":"130","author":"Riggle","year":"2020","journal-title":"J Clin Invest"},{"key":"B23","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.molbiopara.2009.03.006","article-title":"Dysregulation of coagulation in cerebral malaria","volume":"166","author":"Moxon","year":"2009","journal-title":"Mol Biochem Parasitol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06067.x","article-title":"von Willebrand factor propeptide in malaria: evidence of acute endothelial cell activation","volume":"133","author":"Hollestelle","year":"2006","journal-title":"Br J Haematol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1086\/380761","article-title":"Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells","volume":"189","author":"Wassmer","year":"2004","journal-title":"J Infect Dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e20201266","DOI":"10.1084\/jem.20201266","article-title":"Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood\u2013brain barrier in cerebral malaria","volume":"218","author":"Adams","year":"2021","journal-title":"J Exp Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2015.00018","article-title":"Correlation of hemorrhage, axonal damage, and blood-tissue barrier disruption in brain and retina of Malawian children with fatal cerebral malaria","volume":"5","author":"Greiner","year":"2015","journal-title":"Front Cell Infect Microbiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1400116","article-title":"Brain swelling and death in children with cerebral malaria","volume":"372","author":"Seydel","year":"2015","journal-title":"N Engl J Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e145823","DOI":"10.1172\/jci.insight.145823","article-title":"Determinants of brain swelling in pediatric and adult cerebral malaria","volume":"6","author":"Sahu","year":"2021","journal-title":"JCI Insight"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2006.08.005","article-title":"Differential var gene transcription in Plasmodium falciparum isolates from patients with cerebral malaria compared to hyperparasitaemia","volume":"150","author":"Kyriacou","year":"2006","journal-title":"Mol Biochem Parasitol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad217","article-title":"Antibody to Plasmodium falciparum Variant Surface Antigens, var Gene Transcription, and ABO Blood Group in Children with Severe or Uncomplicated Malaria","volume":"228","author":"Barua","year":"2023","journal-title":"J Infect Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1086\/653586","article-title":"Differential var gene expression in children with malaria and antidromic effects on host gene expression","volume":"202","author":"Kalmbach","year":"2010","journal-title":"J Infect Dis"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120455109","article-title":"Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children","volume":"109","author":"Lavstsen","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040274","article-title":"Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes","volume":"199","author":"Jensen","year":"2004","journal-title":"J Exp Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e1004537","DOI":"10.1371\/journal.ppat.1004537","article-title":"Differential PfEMP1 expression is associated with cerebral malaria pathology","volume":"10","author":"Tembo","year":"2014","journal-title":"PloS Pathog"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907590106","article-title":"Plasmodium falciparum var gene expression is modified by host immunity","volume":"106","author":"Warimwe","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.11.007","article-title":"Structural conservation despite huge sequence diversity allows EPCR binding by the pfEMP1 family implicated in severe childhood malaria","volume":"17","author":"Lau","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.02.009","article-title":"Structure-guided identification of a family of dual receptor-binding pfEMP1 that is associated with cerebral malaria","volume":"21","author":"Lennartz","year":"2017","journal-title":"Cell Host Microbe"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00217-19","article-title":"Meta-analysis of Plasmodium falciparum var Signatures Contributing to Severe Malaria in African Children and Indian Adults","volume":"10","author":"Duffy","year":"2019","journal-title":"mBio"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.09.009","article-title":"Linking EPCR-binding PfEMP1 to brain swelling in pediatric cerebral malaria","volume":"22","author":"Kessler","year":"2017","journal-title":"Cell Host Microbe"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e9164","DOI":"10.15252\/emmm.201809164","article-title":"Cerebral malaria is associated with differential cytoadherence to brain endothelial cells","volume":"11","author":"Storm","year":"2019","journal-title":"EMBO Mol Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nature12216","article-title":"Severe malaria is associated with parasite binding to endothelial protein C receptor","volume":"498","author":"Turner","year":"2013","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","first-page":"e1002032","DOI":"10.1371\/journal.ppat.1002032","article-title":"Investigating the host binding signature on the plasmodium falciparum pfEMP1 protein family","volume":"7","author":"Janes","year":"2011","journal-title":"PloS Pathog"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040545897","article-title":"Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria","volume":"97","author":"Smith","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00615-16","article-title":"Interaction between endothelial protein C receptor and intercellular adhesion molecule 1 to mediate binding of plasmodium falciparum-infected erythrocytes to endothelial cells","volume":"7","author":"Avril","year":"2016","journal-title":"mBio"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix230","article-title":"Parasites causing cerebral falciparum malaria bind multiple endothelial receptors and express EPCR and ICAM1-binding pfEMP1","volume":"215","author":"Tuikue Ndam","year":"2017","journal-title":"J Infect Dis"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1524294113","article-title":"Severe adult malaria is associated with specific PfEMP1 adhesion types and high parasite biomass","volume":"113","author":"Bernabeu","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B48","doi-asserted-by":"publisher","first-page":"e68368","DOI":"10.1371\/journal.pone.0068368","article-title":"Expression of the domain cassette 8 Plasmodium falciparum erythrocyte membrane protein 1 is associated with cerebral malaria in Benin","volume":"8","author":"Bertin","year":"2013","journal-title":"PloS One"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606188","article-title":"Plasmodium falciparum var genes expressed in children with severe malaria encode CIDR\u03b11 domains","volume":"8","author":"Jespersen","year":"2016","journal-title":"EMBO Mol Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00841-16","article-title":"The Severity of Plasmodium falciparum Infection Is Associated with Transcript Levels of var Genes Encoding Endothelial Protein C Receptor-Binding P. falciparum Erythrocyte Membrane Protein 1","volume":"85","author":"Mkumbaye","year":"2017","journal-title":"Infect Immun"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/srep18034","article-title":"Differential Plasmodium falciparum surface antigen expression among children with Malarial Retinopathy","volume":"5","author":"Abdi","year":"2015","journal-title":"Sci Rep"},{"key":"B52","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s12916-017-0945-y","article-title":"Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria disease severity and is elevated in retinopathy negative cerebral malaria","volume":"15","author":"Shabani","year":"2017","journal-title":"BMC Med"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e26","DOI":"10.1371\/journal.ppat.0010026","article-title":"Plasmodium falciparum variant surface antigen expression patterns during malaria","volume":"1","author":"Bull","year":"2005","journal-title":"PloS Pathog"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.9.5849-5856.2001","article-title":"Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors","volume":"69","author":"Heddini","year":"2001","journal-title":"Infect Immun"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10010031","article-title":"Differential expression of CD31 and von willebrand factor on endothelial cells in different regions of the human brain: potential implications for cerebral malaria pathogenesis","volume":"10","author":"Mbagwu","year":"2020","journal-title":"Brain Sci"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/s1383-5769(01)00082-4","article-title":"Association of adhesion molecule PECAM-1\/CD31 polymorphism with susceptibility to cerebral malaria in Thais","volume":"50","author":"Kikuchi","year":"2001","journal-title":"Parasitol Int"},{"key":"B57","first-page":"87","article-title":"Association of PECAM1\/CD31 polymorphisms with cerebral malaria","volume":"7","author":"Ohashi","year":"2016","journal-title":"Int J Mol Epidemiol Genet"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1992.46.503","article-title":"Rosette formation in Plasmodium falciparum isolates and anti-rosette activity of sera from Gambians with cerebral or uncomplicated malaria","volume":"46","author":"Treutiger","year":"1992","journal-title":"Am J Trop Med Hyg"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.6.2323-2326.1995","article-title":"Plasmodium falciparum rosetting is associated with malaria severity in Kenya","volume":"63","author":"Rowe","year":"1995","journal-title":"Infect Immun"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2009.09-0406","article-title":"High levels of Plasmodium falciparum rosetting in all clinical forms of severe malaria in African children","volume":"81","author":"Doumbo","year":"2009","journal-title":"Am J Trop Med Hyg"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)93174-n","article-title":"Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies","volume":"336","author":"Carlson","year":"1990","journal-title":"Lancet"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(95)90658-4","article-title":"Human cerebral malaria: lack of significant association between erythrocyte rosetting and disease severity","volume":"89","author":"Al-Yaman","year":"1995","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1086\/381900","article-title":"Platelet-induced autoagglutination of Plasmodium falciparum-infected red blood cells and disease severity in Thailand","volume":"189","author":"Chotivanich","year":"2004","journal-title":"J Infect Dis"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.21-1229","article-title":"Rosetting responses of plasmodium-infected erythrocytes to antimalarials","volume":"106","author":"Lee","year":"2022","journal-title":"Am J Trop Med Hyg"},{"key":"B65","doi-asserted-by":"publisher","first-page":"e51546","DOI":"10.7554\/eLife.51546","article-title":"Plasmodium-infected erythrocytes induce secretion of IGFBP7 to form type II rosettes and escape phagocytosis","volume":"9","author":"Lee","year":"2020","journal-title":"Elife"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103680","article-title":"Plasmodium falciparum rosetting protects schizonts against artemisinin","volume":"73","author":"Lee","year":"2021","journal-title":"EBioMedicine"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2022.08.001","article-title":"Evolving perspectives on rosetting in malaria","volume":"38","author":"Lee","year":"2022","journal-title":"Trends Parasitol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S0031182019001288","article-title":"Parasitology Rosetting revisited: a critical look at the evidence for host erythrocyte receptors in Plasmodium falciparum rosetting","volume":"147","author":"Mcquaid","year":"2019","journal-title":"Plasmodium Falciparum Rosetting Parasitol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"e1002781","DOI":"10.1371\/journal.ppat.1002781","article-title":"Structural basis for the ABO blood-group dependence of plasmodium falciparum rosetting","volume":"8","author":"Vigan-Womas","year":"2012","journal-title":"PloS Pathog"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2020.12.008","article-title":"Bioengineered 3D microvessels for investigating plasmodium falciparum pathogenesis","volume":"37","author":"Bernabeu","year":"2021","journal-title":"Trends Parasitol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/40888","article-title":"falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1","volume":"388","author":"Rowe","year":"1997","journal-title":"Nature"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-17","article-title":"Var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2","volume":"10","author":"Albrecht","year":"2011","journal-title":"Malar J"},{"key":"B73","doi-asserted-by":"publisher","first-page":"e1002665","DOI":"10.1371\/journal.ppat.1002665","article-title":"Induction of strain-transcending antibodies against group A pfEMP1 surface antigens from virulent malaria parasites","volume":"8","author":"Ghumra","year":"2012","journal-title":"PloS Pathog"},{"key":"B74","doi-asserted-by":"publisher","first-page":"e16544","DOI":"10.1371\/journal.pone.0016544","article-title":"Allelic diversity of the plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes","volume":"6","author":"Vigan-Womas","year":"2011","journal-title":"PloS One"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012434","article-title":"Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype","volume":"21","author":"McLean","year":"2025","journal-title":"PloS Pathog"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy580","article-title":"Antibody targets on the surface of plasmodium falciparum- infected erythrocytes that are associated with immunity to severe malaria in young children","volume":"219","author":"Chan","year":"2019","journal-title":"J Infect Dis"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.2.733-739.1999","article-title":"Antibody recognition of plasmodium falciparum erythrocyte surface antigens in Kenya: evidence for rare and prevalent variants","volume":"67","author":"Bull","year":"1999","journal-title":"Infect Immun"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00593-10","article-title":"Hierarchical, domain type-specific acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 in Tanzanian children","volume":"78","author":"Cham","year":"2010","journal-title":"Infect Immun"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00224-19","article-title":"Acquisition of IGG to ICAM1-Binding DBL\u03b2 Domains in the plasmodium falciparum erythrocyte membrane protein 1 antigen family varies between groups A, B and C","volume":"87","author":"Olsen","year":"2019","journal-title":"Infect Immun"},{"key":"B80","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/j.1365-3024.2006.00808.x","article-title":"Immune effector mechanisms in malaria","volume":"28","author":"Marsh","year":"2006","journal-title":"Parasite Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2024.106252","article-title":"Antibodies to PfEMP1 and variant surface antigens: Protection after controlled human malaria infection in semi-immune Kenyan adults","volume":"89","author":"Kinyua","year":"2024","journal-title":"J Infect"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30066-5","article-title":"Burden, pathology, and costs of malaria in pregnancy: new developments for an old problem","volume":"18","author":"Rogerson","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1086\/315652","article-title":"Plasmodium falciparum-infected erythrocytes: Agglutination by diverse Kenyan plasma is associated with severe disease and young host age","volume":"182","author":"Bull","year":"2000","journal-title":"J Infect Dis"},{"key":"B84","article-title":"Antibodies to Intercellular Adhesion Molecule 1-Binding Plasmodium falciparum Erythrocyte Membrane Protein 1-DBL Are Biomarkers of Protective Immunity to Malaria in a Cohort of Young Children from Papua New Guinea","volume-title":"Infect Immun","author":"Tessema","year":"2018"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa043","article-title":"The journal of infectious diseases dynamics of pfEMP1 antibody profile from birth to 12 months of age in Beninese infants","volume":"221","author":"Moussiliou","year":"2020","journal-title":"J Infect Dis"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.137262","article-title":"Longitudinal analysis of naturally acquired PfEMP1 CIDR domain variant antibodies identifies associations with malaria protection","volume":"5","author":"Obeng-Adjei","year":"2020","journal-title":"JCI Insight"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00271-15","article-title":"IgG antibodies to endothelial protein C receptor-binding cysteine-rich interdomain region domains of Plasmodium falciparum erythrocyte membrane protein 1 are acquired early in life in individuals exposed to malaria","volume":"83","author":"Turner","year":"2015","journal-title":"Infect Immun"},{"key":"B88","doi-asserted-by":"publisher","first-page":"e2004328","DOI":"10.1371\/journal.pbio.2004328","article-title":"The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes","volume":"16","author":"Tonkin-Hill","year":"2018","journal-title":"PloS Biol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/nm0398-358","article-title":"Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria","volume":"4","author":"Bull","year":"1998","journal-title":"Nat Med"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62182","article-title":"Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity","volume":"122","author":"Chan","year":"2012","journal-title":"J Clin Invest"},{"key":"B91","doi-asserted-by":"publisher","first-page":"6281","DOI":"10.1038\/s41598-018-24462-4","article-title":"Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets","volume":"8","author":"Travassos","year":"2018","journal-title":"Sci Rep"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy564","article-title":"Acquisition of antibodies against endothelial protein C receptor-binding domains of plasmodium falciparum erythrocyte membrane protein 1 in children with severe malaria","volume":"219","author":"Rambhatla","year":"2019","journal-title":"J Infect Dis"},{"key":"B93","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1186\/s12936-015-1008-5","article-title":"Beninese children with cerebral malaria do not develop humoral immunity against the IT4-VAR19-DC8 PfEMP1 variant linked to EPCR and brain endothelial binding","volume":"8","author":"Nunes-Silva","year":"2015","journal-title":"Malar J"},{"key":"B94","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1186\/s12936-024-05196-3","article-title":"Severe falciparum malaria in young children is associated with an increased risk of post-discharge readmission or death: A prospective cohort study","volume":"23","author":"Opoka","year":"2024","journal-title":"Malar J"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00435-21","article-title":"Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1","volume":"90","author":"Rambhatla","year":"2022","journal-title":"Infect Immun"},{"key":"B96","doi-asserted-by":"publisher","first-page":"3680","DOI":"10.1038\/s41598-021-82444-5","article-title":"IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBL\u03b23_D4 domain, and peptides located within these constructs in children with cerebral malaria","volume":"11","author":"Badaut","year":"2021","journal-title":"Sci Rep"},{"key":"B97","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s12936-018-2323-4","article-title":"Convalescent Plasmodium falciparum-specific seroreactivity does not correlate with paediatric malaria severity or Plasmodium antigen exposure","volume":"17","author":"Kessler","year":"2018","journal-title":"Malar J"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02103-20","article-title":"PfEMP1 A-type ICAM1-binding domains are not associated with cerebral malaria in Beninese children","volume":"11","author":"Joste","year":"2020","journal-title":"mBio"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00622-17","article-title":"Natural and vaccine-induced acquisition of cross-reactive igG-inhibiting ICAM1-specific binding of a plasmodium falciparum pfEMP1 subtype associated specifically with cerebral malaria","volume":"86","author":"Olsen","year":"2018","journal-title":"Infect Immun"},{"key":"B100","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.chom.2019.10.012","article-title":"Protective immunity against severe malaria in children is associated with a limited repertoire of antibodies to conserved pfEMP1 variants","volume":"26","author":"Tessema","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B101","doi-asserted-by":"publisher","first-page":"12994","DOI":"10.1038\/s41598-022-16305-0","article-title":"ICAM1-binding Plasmodium falciparum erythrocyte membrane protein 1 variants elicits opsonic-phagocytosis IgG responses in Beninese children","volume":"12","author":"Suurbaar","year":"2022","journal-title":"Sci Rep"},{"key":"B102","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1186\/s12916-024-03604-8","article-title":"A systems serology approach to identifying key antibody correlates of protection from cerebral malaria in Malawian children","volume":"22","author":"Walker","year":"2024","journal-title":"BMC Med"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.129868","article-title":"Glycophorin B-PfEMP1 interaction mediates robust rosetting in Plasmodium falciparum","volume":"262","author":"Deb","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12403","article-title":"Investigating the function of Fc-specific binding of IgM to Plasmodium falciparum erythrocyte membrane protein 1 mediating erythrocyte rosetting","volume":"17","author":"Stevenson","year":"2015","journal-title":"Cell Microbiol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad438","article-title":"Profiling the plasmodium falciparum erythrocyte membrane protein 1-specific immununoglobulin G response among Ghanaian children with hemoglobin S and C","volume":"229","author":"Oleinikov","year":"2024","journal-title":"J Infect Dis"},{"key":"B106","doi-asserted-by":"publisher","first-page":"e36806","DOI":"10.7554\/eLife.36806","article-title":"NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity","volume":"7","author":"Arora","year":"2018","journal-title":"Elife"},{"key":"B107","doi-asserted-by":"publisher","first-page":"5838","DOI":"10.1038\/s41467-021-26118-w","article-title":"Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination","volume":"12","author":"Larsen","year":"2021","journal-title":"Nat Commun"},{"key":"B108","doi-asserted-by":"publisher","first-page":"eadd9012","DOI":"10.1126\/scitranslmed.add9012","article-title":"Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria","volume":"15","author":"Ty","year":"2023","journal-title":"Sci Transl Med"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2021.1981864","article-title":"Multi-functional antibody profiling for malaria vaccine development and evaluation","volume":"20","author":"Opi","year":"2021","journal-title":"Expert Rev Vaccines"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.683404","article-title":"Beyond binding: the outcomes of antibody-dependent complement activation in human malaria","volume":"12","author":"Rathnayake","year":"2021","journal-title":"Front Immunol"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03088","article-title":"Evasion of classical complement pathway activation on Plasmodium falciparum-infected erythrocytes opsonized by PfEMP1-Specific IgG","volume":"9","author":"Larsen","year":"2019","journal-title":"Front Immunol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-9-267","article-title":"The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children","volume":"9","author":"Vigan-Womas","year":"2010","journal-title":"Malar J"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.5.2848-2856.2005","article-title":"Cross-reactive surface epitopes on chondroitin sulfate A-adherent Plasmodium falciparum-infected erythrocytes are associated with transcription of var2csa","volume":"73","author":"Elliott","year":"2005","journal-title":"Infect Immun"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1126\/science.1248943","article-title":"Complement is activated by IgG hexamers assembled at the cell surface","volume":"343","author":"Diebolder","year":"2014","journal-title":"Science"},{"key":"B115","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/s42003-021-02511-5","article-title":"Neutrophils dominate in opsonic phagocytosis of P. falciparum blood-stage merozoites and protect against febrile malaria","volume":"4","author":"Garcia-Senosiain","year":"2021","journal-title":"Commun Biol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1038\/s41467-021-21998-4","article-title":"Mechanisms and targets of Fc\u03b3-receptor mediated immunity to malaria sporozoites","volume":"12","author":"Feng","year":"2021","journal-title":"Nat Commun"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202069200","article-title":"Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity","volume":"277","author":"Shields","year":"2002","journal-title":"J Biol Chem"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00877","article-title":"Decoding the human immunoglobulin G-glycan repertoire reveals a spectrum of fc-receptor- and complement-mediated-effector activities","volume":"8","author":"Dekkers","year":"2017","journal-title":"Front Immunol"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2022.08.001","article-title":"Afucosylated IgG responses in humans \u2013 structural clues to the regulation of humoral immunity","volume":"43","author":"Oosterhoff","year":"2022","journal-title":"Trends Immunol"},{"key":"B120","doi-asserted-by":"publisher","first-page":"1","DOI":"10.21203\/rs.3.rs-4165378\/v1","article-title":"Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria","volume":"16","author":"Lopez-Perez","year":"2024","journal-title":"Nat Commun"},{"key":"B121","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1128\/CVI.00564-15","article-title":"Lymphocyte perturbations in Malawian children with severe and uncomplicated malaria","volume":"23","author":"Mandala","year":"2015","journal-title":"Clin Vaccine Immunol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00449","article-title":"Regulation of Fc receptor endocytic trafficking by ubiquitination","volume":"5","author":"Molfetta","year":"2014","journal-title":"Front Immunol"},{"key":"B123","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10337-019-03796-9","article-title":"Current trends in the analysis of post-translational modifications","volume":"83","author":"Vir\u00e1g","year":"2020","journal-title":"Chromatographia"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2021.2023938","article-title":"In silico prediction of post-translational modifications in therapeutic antibodies","volume":"14","author":"Vatsa","year":"2022","journal-title":"MAbs"},{"key":"B125","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1038\/s41586-024-08220-3","article-title":"Broadly inhibitory antibodies to severe malaria virulence proteins","volume":"2024","author":"Reyes","year":"8041","journal-title":"Nature"},{"key":"B126","doi-asserted-by":"publisher","first-page":"e76264","DOI":"10.7554\/eLife.76264","article-title":"A single full-length VAR2CSA ectodomain variant purifies broadly neutralizing antibodies against placental malaria isolates","volume":"11","author":"Doritchamou","year":"2022","journal-title":"eLife"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1038\/357689a0","article-title":"Rapid switching to multiple antigenic and adhesive phenotypes in malaria","volume":"357","author":"Roberts","year":"1992","journal-title":"Nature"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202153641","article-title":"Neutrophils impose strong immune pressure against PfEMP1 variants implicated in cerebral malaria","volume":"23","author":"Zelter","year":"2022","journal-title":"EMBO Rep"},{"key":"B129","doi-asserted-by":"publisher","first-page":"e0295053","DOI":"10.1371\/journal.pone.0295053","article-title":"Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture","volume":"18","author":"Othman","year":"2023","journal-title":"PloS One"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2189-9_36","article-title":"Analysis of antibody inhibition of pfEMP1 binding by competition ELISA","volume":"2470","author":"Olsen","year":"2022","journal-title":"Methods Mol Biol"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2189-9_43","article-title":"Binding of plasmodium falciparum-infected red blood cells to engineered 3D microvessels","volume":"2470","author":"Piatti","year":"2022","journal-title":"Methods Mol Biol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00420-19","article-title":"Binding heterogeneity of plasmodium falciparum to engineered 3D brain microvessels is mediated by EPCR and ICAM1","volume":"10","author":"Bernabeu","year":"2019","journal-title":"mBio"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113253","article-title":"Probing cerebral malaria inflammation in 3D human brain microvessels","volume":"42","author":"Howard","year":"2023","journal-title":"Cell Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1681852\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:23:13Z","timestamp":1761805393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1681852\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":133,"alternative-id":["10.3389\/fimmu.2025.1681852"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1681852","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]},"article-number":"1681852"}}