{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:57:05Z","timestamp":1785427025568,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,8]]},"group-title":"Microbiology","reference-count":100,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["INV-004923"],"award-info":[{"award-number":["INV-004923"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-056202"],"award-info":[{"award-number":["INV-056202"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"name":"USAID","award":["7200AA20C00017"],"award-info":[{"award-number":["7200AA20C00017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The\n                  <jats:italic>Plasmodium falciparum<\/jats:italic>\n                  circumsporozoite protein (\n                  <jats:italic>Pf<\/jats:italic>\n                  CSP) is the major surface antigen on\n                  <jats:italic>Pf<\/jats:italic>\n                  sporozoites. WHO-recommended vaccines RTS,S\/AS01\n                  <jats:sub>E<\/jats:sub>\n                  and R21\/Matrix-M target the\n                  <jats:italic>Pf<\/jats:italic>\n                  CSP major repeat region and C-terminal domain (ctCSP). Although multiple studies associated protection with antibody responses to ctCSP, only a few ctCSP-specific monoclonal antibodies (mAbs) have been characterized. Here, crystal structures of 11 Fab-ctCSP complexes reveal how mAbs against the conserved \u03b2-epitope region achieve diverse modes of strain-transcending recognition, in contrast to mAbs to the hypervariable \u237a-epitope. Consistent with previous studies, ctCSP on sporozoites could be unmasked by mAbs that bind CSP repeats, with unmasking dependent on the mAb fine-specificity and binding mode. In vitro, ctCSP mAbs promoted stronger Fc-receptor signaling, cellular cytotoxicity, and phagocytosis than repeat region mAbs, while mAb combinations targeting distinct\n                  <jats:italic>Pf<\/jats:italic>\n                  CSP epitopes modulated Fc-signaling and cellular cytotoxicity. This study provides a rationale for optimization of\n                  <jats:italic>Pf<\/jats:italic>\n                  CSP-based immunogens to enhance Fc-mediated contributions to malaria vaccine efficacy.\n                <\/jats:p>","DOI":"10.64898\/2026.06.06.730512","type":"posted-content","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T03:50:18Z","timestamp":1780977018000},"source":"Crossref","is-referenced-by-count":0,"title":["Structure and functional diversity of antibodies targeting the\n                  <i>P. falciparum<\/i>\n                  circumsporozoite protein C-terminal domain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6091-1285","authenticated-orcid":false,"given":"Re\u2019em","family":"Moskovitz","sequence":"first","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6713-8805","authenticated-orcid":false,"given":"Iszac","family":"Burton","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3240-9524","authenticated-orcid":false,"given":"Nathan","family":"Beutler","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4708-5753","authenticated-orcid":false,"given":"Gonzalo","family":"Gonzalez-Paez","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6021-3740","authenticated-orcid":false,"given":"Xueyong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8700-4562","authenticated-orcid":false,"given":"Monika","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-2113","authenticated-orcid":false,"given":"Elizabeth A","family":"Winzeler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E","family":"Emerling","sequence":"additional","affiliation":[{"name":"Atreca, Inc., San Carlos, CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-3760","authenticated-orcid":false,"given":"Christian F","family":"Ockenhouse","sequence":"additional","affiliation":[{"name":"PATH\u2019s Center for Vaccine Innovation and Access, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4566-1481","authenticated-orcid":false,"given":"Randall S","family":"MacGill","sequence":"additional","affiliation":[{"name":"PATH\u2019s Center for Vaccine Innovation and Access, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Locke","sequence":"additional","affiliation":[{"name":"PATH\u2019s Center for Vaccine Innovation and 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