{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:20:08Z","timestamp":1788409208183,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013950","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000}}],"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI164698"],"award-info":[{"award-number":["R01AI164698"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["55108533"],"award-info":[{"award-number":["55108533"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31AI179031"],"award-info":[{"award-number":["F31AI179031"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Human cytomegalovirus (HCMV) poses a significant risk to immunocompromised individuals and is the leading cause of congenital birth defects worldwide. There is no cure or robust treatment options, although neutralizing antibodies (nAbs) derived from patient sera are being explored as prophylactics with limited success. Glycoprotein B (gB) is a viral membrane fusogen and a major target of the anti-HCMV humoral response in humans. Here, we engineered a soluble, prefusion-stabilized HCMV gB ectodomain variant and used it to isolate twelve new human monoclonal antibodies (mAbs). Seven of these mAbs strongly neutralized at least one strain of HCMV\n                    <jats:italic>in vitro,<\/jats:italic>\n                    whereas six mAbs neutralized both lab-adapted and minimally passaged clinical strains (were broadly neutralizing, bnAbs). All nAbs bound different epitopes within antigenic regions AD-4 or AD-5, and most targeted new sites. Despite being isolated using prefusion-stabilized HCMV gB variant, nAbs varied in their conformational specificity. Only one nAb preferentially bound the prefusion form, and most preferentially bound the intermediate form. The seven nAbs were separated into three classes based on their putative neutralization mechanisms, which were deduced from their conformational specificity, reactivity with gB on the cell surface, and epitope location. Our stabilized prefusion-gB construct provides a tool for isolating potent new nAbs, including prefusion-specific ones, and studying HCMV immunogenicity. Long term, these potent nAbs that arose during natural infections could be developed into potent prophylactics and therapeutics against HCMV diseases.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013950","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T18:48:35Z","timestamp":1770317315000},"page":"e1013950","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Isolation and characterization of broadly-neutralizing anti-HCMV-gB antibodies from human donors using a prefusion-stabilized HCMV gB variant"],"prefix":"10.1371","volume":"22","author":[{"given":"Maria K.","family":"McClave","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsin","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"G\u00e1lvez Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Karimian Shamsabadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Aldridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibhav","family":"Poudel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian W.","family":"Sperl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T.","family":"McGuire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3113-6958","authenticated-orcid":true,"given":"Ekaterina E.","family":"Heldwein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"issue":"2","key":"ppat.1013950.ref001","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00430-007-0066-x","article-title":"The history of cytomegalovirus and its diseases","volume":"197","author":"M Ho","year":"2008","journal-title":"Med Microbiol Immunol"},{"key":"ppat.1013950.ref002","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1743-422X-6-4","article-title":"Feeling manipulated: cytomegalovirus immune manipulation","volume":"6","author":"M Miller-Kittrell","year":"2009","journal-title":"Virol J"},{"issue":"3","key":"ppat.1013950.ref003","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2217\/fvl.12.8","article-title":"The immune response to human CMV","volume":"7","author":"C La Rosa","year":"2012","journal-title":"Future Virol"},{"issue":"4","key":"ppat.1013950.ref004","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1542\/pir.33.4.156","article-title":"Cytomegalovirus infection","volume":"33","author":"EJ Plosa","year":"2012","journal-title":"Pediatr Rev"},{"issue":"9","key":"ppat.1013950.ref005","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2807\/ese.14.09.19140-en","article-title":"Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe","volume":"14","author":"A Ludwig","year":"2009","journal-title":"Euro Surveill"},{"issue":"4","key":"ppat.1013950.ref006","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/rmv.535","article-title":"Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection","volume":"17","author":"A Kenneson","year":"2007","journal-title":"Rev Med Virol"},{"key":"ppat.1013950.ref007","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.coviro.2017.04.006","article-title":"The COMPLEXity in herpesvirus entry","volume":"24","author":"K Sathiyamoorthy","year":"2017","journal-title":"Curr Opin Virol"},{"key":"ppat.1013950.ref008","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.coviro.2018.05.004","article-title":"From recognition to execution-the HCMV Pentamer from receptor binding to fusion triggering","volume":"31","author":"E Malito","year":"2018","journal-title":"Curr Opin Virol"},{"issue":"12","key":"ppat.1013950.ref009","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3390\/v10120704","article-title":"Pathogen at the gates: human cytomegalovirus entry and cell tropism","volume":"10","author":"CC Nguyen","year":"2018","journal-title":"Viruses"},{"issue":"2","key":"ppat.1013950.ref010","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3390\/v14020296","article-title":"Well put together-a guide to accessorizing with the herpesvirus gH\/gL complexes","volume":"14","author":"GL Gonzalez-Del Pino","year":"2022","journal-title":"Viruses"},{"issue":"23","key":"ppat.1013950.ref011","doi-asserted-by":"crossref","first-page":"11837","DOI":"10.1128\/JVI.01623-08","article-title":"Human cytomegalovirus glycoproteins gB and gH\/gL mediate epithelial cell-cell fusion when expressed either in cis or in trans","volume":"82","author":"AL Vanarsdall","year":"2008","journal-title":"J Virol"},{"issue":"18","key":"ppat.1013950.ref012","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01276-20","article-title":"Cell fusion induced by a fusion-active form of human cytomegalovirus glycoprotein B (gB) is inhibited by antibodies directed at antigenic domain 5 in the Ectodomain of gB","volume":"94","author":"N Reuter","year":"2020","journal-title":"J Virol"},{"issue":"2","key":"ppat.1013950.ref013","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1006\/viro.1993.1192","article-title":"Initiation of human cytomegalovirus infection requires initial interaction with cell surface heparan sulfate","volume":"193","author":"T Compton","year":"1993","journal-title":"Virology"},{"issue":"50","key":"ppat.1013950.ref014","doi-asserted-by":"crossref","first-page":"18153","DOI":"10.1073\/pnas.0509201102","article-title":"Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism","volume":"102","author":"D Wang","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1013950.ref015","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1128\/JVI.01910-07","article-title":"Characterization of the human cytomegalovirus gH\/gL\/UL128-131 complex that mediates entry into epithelial and endothelial 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Norris","year":"2025","journal-title":"Nat Microbiol"},{"issue":"8","key":"ppat.1013950.ref019","doi-asserted-by":"crossref","first-page":"16082","DOI":"10.1038\/nmicrobiol.2016.82","article-title":"Platelet-derived growth factor-\u03b1 receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer","volume":"1","author":"A Kabanova","year":"2016","journal-title":"Nat Microbiol"},{"issue":"4","key":"ppat.1013950.ref020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1006273","article-title":"A derivative of platelet-derived growth factor receptor alpha binds to the trimer of human cytomegalovirus and inhibits entry into fibroblasts and endothelial cells","volume":"13","author":"C Stegmann","year":"2017","journal-title":"PLoS Pathog"},{"issue":"42","key":"ppat.1013950.ref021","article-title":"Role of PDGF receptor-\u03b1 during human cytomegalovirus entry into fibroblasts","volume":"115","author":"K Wu","year":"2018","journal-title":"Proc Natl Acad Sci U S 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sequence of more than 70 amino acids is essential for antibody binding to the dominant antigenic site of glycoprotein gp58 of human cytomegalovirus","volume":"66","author":"B Wagner","year":"1992","journal-title":"J Virol"},{"key":"ppat.1013950.ref032","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1099\/0022-1317-71-10-2443","article-title":"The gp116 of the gp58\/116 complex of human cytomegalovirus represents the amino-terminal part of the precursor molecule and contains a neutralizing epitope","author":"H Meyer","year":"1990","journal-title":"J Gen Virol"},{"key":"ppat.1013950.ref033","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1099\/0022-1317-73-9-2375","article-title":"Glycoprotein gp116 of human cytomegalovirus contains epitopes for strain-common and strain-specific antibodies","author":"H Meyer","year":"1992","journal-title":"J Gen 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Crank","year":"2019","journal-title":"Science"},{"issue":"9","key":"ppat.1013950.ref040","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1016\/j.vaccine.2019.10.046","article-title":"Updates on immunologic correlates of vaccine-induced protection","volume":"38","author":"SA Plotkin","year":"2020","journal-title":"Vaccine"},{"issue":"7","key":"ppat.1013950.ref041","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1128\/CVI.00131-10","article-title":"Correlates of protection induced by vaccination","volume":"17","author":"SA Plotkin","year":"2010","journal-title":"Clin Vaccine Immunol"},{"issue":"2","key":"ppat.1013950.ref042","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/infdis\/jiad593","article-title":"Human cytomegalovirus mRNA-1647 vaccine candidate elicits potent and broad neutralization and higher antibody-dependent cellular cytotoxicity responses than the gB\/MF59 vaccine","volume":"230","author":"X Hu","year":"2024","journal-title":"J Infect Dis"},{"issue":"6","key":"ppat.1013950.ref043","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1093\/cid\/ciz1036","article-title":"The value of hyperimmune globulin in pregnancies complicated by cytomegalovirus infection: a continuing saga","volume":"71","author":"MR Schleiss","year":"2020","journal-title":"Clin Infect Dis"},{"key":"ppat.1013950.ref044","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.antiviral.2018.09.003","article-title":"New therapies for human cytomegalovirus infections","volume":"159","author":"WJ Britt","year":"2018","journal-title":"Antiviral Res"},{"issue":"6158","key":"ppat.1013950.ref045","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1126\/science.1243283","article-title":"Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus","volume":"342","author":"JS 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stability of its postfusion form","volume":"425","author":"E Vitu","year":"2013","journal-title":"J Mol Biol"},{"issue":"39","key":"ppat.1013950.ref061","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abc1726","article-title":"The prefusion structure of herpes simplex virus glycoprotein B","volume":"6","author":"B Vollmer","year":"2020","journal-title":"Sci Adv"},{"issue":"22","key":"ppat.1013950.ref062","doi-asserted-by":"crossref","first-page":"14050","DOI":"10.3390\/ijms232214050","article-title":"Intrinsically disordered proteins: an overview","volume":"23","author":"R Trivedi","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"1","key":"ppat.1013950.ref063","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S1093-3263(00)00138-8","article-title":"Intrinsically disordered protein","volume":"19","author":"AK Dunker","year":"2001","journal-title":"J Mol Graph 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