{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:39:45Z","timestamp":1793723985629,"version":"4.6.1"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["75N93019C00040"],"award-info":[{"award-number":["75N93019C00040"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lyme disease is a tick-borne, multisystem infection caused by the spirochete Borreliella burgdorferi. Although Abs have been implicated in the resolution of Lyme disease, the specific B cell epitopes targeted during human infections remain largely unknown. In this study, we characterized and defined the structural epitope of a patient-derived bactericidal monoclonal IgG (B11) against outer surface protein C (OspC), a homodimeric lipoprotein necessary for B. burgdorferi tick-mediated transmission and early-stage colonization of vertebrate hosts. High-resolution epitope mapping was accomplished through hydrogen deuterium exchange\u2013mass spectrometry and X-ray crystallography. Structural analysis of B11 Fab-OspCA complexes revealed the B11 Fabs associated in a 1:1 stoichiometry with the lateral faces of OspCA homodimers such that the Abs are essentially positioned perpendicular to the spirochete\u2019s outer surface. B11\u2019s primary contacts reside within the membrane-proximal regions of \u03b1-helices 1 and 6 and adjacent loops 5 and 6 in one OspCA monomer. In addition, B11 spans the OspCA dimer interface, engaging opposing \u03b1-helix 1\u2032, \u03b1-helix 2\u2032, and loop 2\u20133\u2032 in the second OspCA monomer. The B11-OspCA structure is reminiscent of the recently solved mouse transmission blocking monoclonal IgG B5 in complex with OspCA, indicating a mode of engagement with OspC that is conserved across species. In conclusion, we provide a detailed insight into the interaction between a functional human Ab and an immunodominant Lyme disease Ag long considered an important vaccine candidate.<\/jats:p>","DOI":"10.4049\/jimmunol.2400247","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T09:31:47Z","timestamp":1725615107000},"page":"1234-1243","source":"Crossref","is-referenced-by-count":5,"title":["Structure of a Human Monoclonal Antibody in Complex with Outer Surface Protein C of the Lyme Disease Spirochete,\n                    <i>Borreliella burgdorferi<\/i>"],"prefix":"10.1093","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-9817","authenticated-orcid":false,"given":"Michael J","family":"Rudolph","sequence":"first","affiliation":[{"name":"New York Structural Biology Center , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6401-1266","authenticated-orcid":false,"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"New York Structural Biology Center , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clint","family":"Vorauer","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Washington , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-7722","authenticated-orcid":false,"given":"David J","family":"Vance","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Wadsworth Center, New York State Department of Health , Albany, NY"},{"name":"Department of Biomedical Sciences, University at Albany , Albany, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol Lyn","family":"Piazza","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Wadsworth Center, New York State Department of Health , Albany, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham G","family":"Willsey","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Wadsworth Center, New York State Department of Health , Albany, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1101-2808","authenticated-orcid":false,"given":"Kathleen","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University at Albany , Albany, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Muriuki","sequence":"additional","affiliation":[{"name":"University of Massachusetts Chan Medical School , Worcester, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1417-8339","authenticated-orcid":false,"given":"Lisa A","family":"Cavacini","sequence":"additional","affiliation":[{"name":"University of Massachusetts Chan Medical School , Worcester, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miklos","family":"Guttman","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Washington , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5083-8640","authenticated-orcid":false,"given":"Nicholas J","family":"Mantis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Wadsworth Center, New York State Department of Health , Albany, NY"},{"name":"Department of Biomedical Sciences, University at Albany , Albany, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"2025020609280184900_r1","doi-asserted-by":"crossref","first-page":"616","DOI":"10.3201\/eid2702.202731","article-title":"Estimating the frequency of Lyme disease diagnoses, United States, 2010\u20132018","volume":"27","author":"Kugeler","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"2025020609280184900_r2","doi-asserted-by":"crossref","first-page":"666554","DOI":"10.3389\/fmed.2021.666554","article-title":"Recent progress in Lyme disease and remaining challenges","volume":"8","author":"Bobe","year":"2021","journal-title":"Front. Med. (Lausanne)"},{"key":"2025020609280184900_r3","first-page":"333","article-title":"Lyme disease in humans","volume":"42","author":"Radolf","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"2025020609280184900_r4","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.1038\/nrdp.2016.90","article-title":"Lyme borreliosis","volume":"2","author":"Steere","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"2025020609280184900_r5","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/s41584-021-00648-5","article-title":"Lyme arthritis: linking infection, inflammation and autoimmunity","volume":"17","author":"Lochhead","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"2025020609280184900_r6","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1056\/NEJM200107123450202","article-title":"Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease","volume":"345","author":"Klempner","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"2025020609280184900_r7","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.idc.2007.12.011","article-title":"Chronic Lyme disease: a review","volume":"22","author":"Marques","year":"2008","journal-title":"Infect. Dis. Clin. North Am."},{"key":"2025020609280184900_r8","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ijid.2022.01.033","article-title":"Risk of post-treatment Lyme disease in patients with ideally-treated early Lyme disease: a prospective cohort study","volume":"116","author":"Aucott","year":"2022","journal-title":"Int. J. Infect. 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