{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:02:24Z","timestamp":1791388944830,"version":"4.3.3"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013740","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["75N93019C00040"],"award-info":[{"award-number":["75N93019C00040"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Lyme disease, caused by the spirochete,\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    sensu latu (Bbsl), is a tickborne infection of increasing incidence in North America, Europe and Asia. While vaccines based on Outer surface protein A (OspA) have proven highly efficacious at blocking Bbsl tick-to-human transmission, the high degree of antigenic variability among the major OspA serotypes (ST) has made the development of a broadly cross protective vaccine difficult. Recent profiling of protective human monoclonal antibodies (mAbs) has suggested the existence of conserved epitopes situated within OspA\u2019s central \u03b2-sheet (CBS), although direct comparisons of cross-serotype functionality has been hindered by biological differences among the major Bbsl genospecies. To address these issues, we developed a panel of isogenic\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    reporter strains expressing the seven major OspA serotypes (ST1\u20137) and probed them with CBS-targeting mAbs to evaluate their complement-dependent borreliacidal activity. The mAbs segregated into three distinct classes: class 1 mAbs exhibited potent killing against all seven OspA serotypes, while classes 2 and 3 had restricted or no activity against two of the seven serotypes. Structural analysis of Fabs derived from each class of mAbs in complex with OspA ST1 showed that they target overlapping epitopes spanning \u03b2-strands 6\u201310 and involve contact with largely invariant residues. Further analysis of\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    reporter strains expressing OspA variants from 17 additional Bbsl genospecies identified Lys-107 as a determinant of susceptibility for nearly all CBS mAbs. Taken together, these findings raise the prospect of structure-based design of a broadly protective monovalent Lyme disease vaccine.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013740","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:51:22Z","timestamp":1776793882000},"page":"e1013740","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Broadly conserved protective epitopes on the lyme disease vaccine antigen, OspA"],"prefix":"10.1371","volume":"22","author":[{"given":"Graham G.","family":"Willsey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rudolph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol Lyn","family":"Piazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Freeman-Gallant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Cavacini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Vance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5083-8640","authenticated-orcid":true,"given":"Nicholas J.","family":"Mantis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"issue":"2","key":"ppat.1013740.ref001","doi-asserted-by":"crossref","first-page":"616","DOI":"10.3201\/eid2702.202731","article-title":"Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018","volume":"27","author":"KJ Kugeler","year":"2021","journal-title":"Emerg Infect Dis"},{"key":"ppat.1013740.ref002","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.1038\/nrdp.2016.90","article-title":"Lyme borreliosis","volume":"2","author":"AC Steere","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"ppat.1013740.ref003","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":"JN Aucott","year":"2022","journal-title":"Int J Infect Dis"},{"issue":"13","key":"ppat.1013740.ref004","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1056\/NEJM198303313081301","article-title":"The spirochetal etiology of Lyme disease","volume":"308","author":"AC Steere","year":"1983","journal-title":"N Engl J Med"},{"issue":"4","key":"ppat.1013740.ref005","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1056\/NEJM199807233390401","article-title":"Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. 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