{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:19:13Z","timestamp":1790306353075,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010999","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000}}],"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-008866"],"award-info":[{"award-number":["INV-008866"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1159947"],"award-info":[{"award-number":["OPP1159947"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-008612"],"award-info":[{"award-number":["INV-008612"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CIFAR Azrieli Global Scholar Program"},{"name":"Ontario Early Researcher Award Program"},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SickKids Restracomp Fellowship"},{"name":"Vanier Canada Graduate Scholarship"},{"name":"SickKids Lap-Chee Tsui Postdoctoral Fellowship"},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Antibodies targeting the human malaria parasite\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    circumsporozoite protein (PfCSP) can prevent infection and disease. PfCSP contains multiple central repeating NANP motifs; some of the most potent anti-infective antibodies against malaria bind to these repeats. Multiple antibodies can bind the repeating epitopes concurrently by engaging into homotypic Fab-Fab interactions, which results in the ordering of the otherwise largely disordered central repeat into a spiral. Here, we characterize\n                    <jats:italic>IGHV3-33\/IGKV1-5<\/jats:italic>\n                    -encoded monoclonal antibody (mAb) 850 elicited by immunization of transgenic mice with human immunoglobulin loci. mAb 850 binds repeating NANP motifs with picomolar affinity, potently inhibits\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    (Pf)\n                    <jats:italic>in vitro<\/jats:italic>\n                    and, when passively administered in a mouse challenge model, reduces liver burden to a similar extent as some of the most potent anti-PfCSP mAbs yet described. Like other\n                    <jats:italic>IGHV3-33\/IGKV1-5<\/jats:italic>\n                    -encoded anti-NANP antibodies, mAb 850 primarily utilizes its HCDR3 and germline-encoded aromatic residues to recognize its core NANP motif. Biophysical and cryo-electron microscopy analyses reveal that up to 19 copies of Fab 850 can bind the PfCSP repeat simultaneously, and extensive homotypic interactions are observed between densely-packed PfCSP-bound Fabs to indirectly improve affinity to the antigen. Together, our study expands on the molecular understanding of repeat-induced homotypic interactions in the B cell response against PfCSP for potently protective mAbs against Pf infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010999","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T13:59:05Z","timestamp":1669643945000},"page":"e1010999","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["High-density binding to Plasmodium falciparum circumsporozoite protein repeats by inhibitory antibody elicited in mouse with human immunoglobulin repertoire"],"prefix":"10.1371","volume":"18","author":[{"given":"Iga","family":"Kucharska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0160pela","family":"Binter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajagopal","family":"Murugan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Scally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Prieto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Thai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian Q.","family":"Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yevel","family":"Flores-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Sicard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Rubinstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fidel","family":"Zavala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Moses","family":"Dennison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia D.","family":"Tomaras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena A.","family":"Levashina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Kellam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedda","family":"Wardemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7602-3995","authenticated-orcid":true,"given":"Jean-Philippe","family":"Julien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"ppat.1010999.ref001","article-title":"World malaria report 2020","author":"World Health Organization","year":"2020","journal-title":"S.l.: WORLD HEALTH ORGANIZATION"},{"issue":"10","key":"ppat.1010999.ref002","first-page":"1691","article-title":"Increased Pyrethroid Resistance in Malaria Vectors and Decreased Bed Net Effectiveness, Burkina Faso","volume":"20","author":"KH To\u00e9","year":"2014","journal-title":"Emerg Infect Dis"},{"issue":"9","key":"ppat.1010999.ref003","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/S1473-3099(19)30392-5","article-title":"Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study","volume":"19","author":"WL Hamilton","year":"2019","journal-title":"The Lancet Infectious Diseases"},{"issue":"6","key":"ppat.1010999.ref004","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/0092-8674(92)90251-7","article-title":"The basolateral domain of the hepatocyte plasma membrane bears receptors for the circumsporozoite protein of Plasmodium falciparum sporozoites","volume":"70","author":"C Cerami","year":"1992","journal-title":"Cell"},{"issue":"5","key":"ppat.1010999.ref005","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1084\/jem.177.5.1287","article-title":"Malaria circumsporozoite protein binds to heparan sulfate proteoglycans associated with the surface membrane of hepatocytes","volume":"177","author":"U Frevert","year":"1993","journal-title":"Journal of Experimental Medicine"},{"issue":"6614","key":"ppat.1010999.ref006","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/385336a0","article-title":"Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes","volume":"385","author":"R M\u00e9nard","year":"1997","journal-title":"Nature"},{"issue":"4662","key":"ppat.1010999.ref007","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1126\/science.6204383","article-title":"Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum","volume":"225","author":"JB Dame","year":"1984","journal-title":"Science"},{"issue":"4662","key":"ppat.1010999.ref008","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1126\/science.6204384","article-title":"DNA cloning of Plasmodium falciparum circumsporozoite gene: amino acid sequence of repetitive epitope","volume":"225","author":"V Enea","year":"1984","journal-title":"Science"},{"issue":"1\u20132","key":"ppat.1010999.ref009","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0166-6851(02)00216-5","article-title":"A study of genetic diversity in the gene encoding the circumsporozoite protein (CSP) of Plasmodium falciparum from different transmission areas\u2014XVI. 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