{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:53:49Z","timestamp":1782280429955,"version":"3.54.5"},"posted":{"date-parts":[[2024,12,21]]},"group-title":"Microbiology","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:00:00Z","timestamp":1734739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R56174062"],"award-info":[{"award-number":["R56174062"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01139258"],"award-info":[{"award-number":["R01139258"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R56174062"],"award-info":[{"award-number":["R56174062"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>BK polyomavirus (BKV) causes polyomavirus-associated nephropathy (BKV-nephropathy) and polyomavirus-associated hemorrhagic cystitis (BKV-HC) following kidney transplantation and allogeneic hematopoietic stem cell transplantation (HSCT). BKV strains consist of four distinct genotypes (BKV-I, - II, -III, and -IV) with more than 80% of individuals seropositive for the BKV-I genotype, and lower prevalences of infection or co-infection with the other genotypes. BKV-nephropathy occurs widely in immunosuppressed transplant recipients, with the recommended treatment including reduction of immunosuppressive drugs. High serum titers of BKV-neutralizing antibodies and treatment with BKV-neutralizing intravenous immunoglobulin (IVIG) are associated with reduced levels of BKV-DNAemia in kidney transplant recipients, suggesting anti-BKV antibodies can limit viral load. Thus, we set out to generate broadly neutralizing human monoclonal antibodies (mAbs) against the viral protein 1 (VP1) major capsid protein of BKV genotypes I-IV using VelocImmune\u00ae transgenic mice that encode for human immunoglobulins. Hybridoma clones from VelocImmune\u00ae mice immunized with combinations of BKV I-IV VP1 and respective genotypes of BKV pseudoviruses (BK-PsV) were screened using a high-throughput binding assay against BKV-I VP1 expressed in HEK-293 cells. The VP1-binding hybridoma clones were then assessed for neutralization with BK-PsV consisting of respective VP1 proteins from BKV-I, -II, -III, or -IV on the virion surface. Overall, thirty-six broadly cross-neutralizing mAbs against BKV-I, -II, -III, and -IV -were identified. Twenty of the cross-reactive immunoglobulins were subjected to nucleotide sequencing resulting in six clonotype families with fourteen genetically distinct immunoglobulins. Several of the most effective mAbs were fully humanized with the IgG1 Fc domain and broad neutralization of BK-PsV-I, II, III, and IV genotypes with IC50s ranging from \u223c7-200 pM. Thus, these cross-neutralizing mAbs represent potential biologics to developed into BKV therapeutics.<\/jats:p>","DOI":"10.1101\/2024.12.18.629307","type":"posted-content","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T10:10:24Z","timestamp":1734775824000},"source":"Crossref","is-referenced-by-count":0,"title":["Broadly neutralizing human monoclonal antibodies against BK polyomavirus genotypes"],"prefix":"10.64898","author":[{"given":"J. Andrew","family":"Duty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhu","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolo A.","family":"Tortorella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tajudeen O.","family":"Jimoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma B.","family":"Barrall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-5665","authenticated-orcid":false,"given":"Diana V.","family":"Pastrana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3165-8094","authenticated-orcid":false,"given":"Christopher B.","family":"Buck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Moran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0961-3535","authenticated-orcid":false,"given":"Domenico","family":"Tortorella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025120510063770000_2024.12.18.629307v2.1","doi-asserted-by":"crossref","first-page":"1263983","DOI":"10.3389\/fcimb.2023.1263983","article-title":"BK polyomavirus: latency, reactivation, diseases and tumorigenesis","volume":"13","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"2025120510063770000_2024.12.18.629307v2.2","doi-asserted-by":"publisher","DOI":"10.3390\/v9110327"},{"key":"2025120510063770000_2024.12.18.629307v2.3","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1146\/annurev-virology-031413-085417","article-title":"Glycan Engagement by Viruses: Receptor Switches and Specificity","volume":"1","year":"2014","journal-title":"Annu Rev Virol"},{"key":"2025120510063770000_2024.12.18.629307v2.4","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01189-13"},{"key":"2025120510063770000_2024.12.18.629307v2.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.10.027"},{"key":"2025120510063770000_2024.12.18.629307v2.6","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.83611-0"},{"key":"2025120510063770000_2024.12.18.629307v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.12.015"},{"key":"2025120510063770000_2024.12.18.629307v2.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2019.104210"},{"key":"2025120510063770000_2024.12.18.629307v2.9","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1097\/TP.0000000000003801","article-title":"Polyoma BK Virus in Kidney Transplant Recipients: Screening, Monitoring, and Management","volume":"106","year":"2022","journal-title":"Transplantation"},{"key":"2025120510063770000_2024.12.18.629307v2.10","doi-asserted-by":"crossref","unstructured":"Nourie N , Boueri C , Tran Minh H , Divard G , Lefaucheur C , Salmona M , Gressens SB , Louis K . 2024. BK Polyomavirus Infection in Kidney Transplantation: A Comprehensive Review of Current Challenges and Future Directions. Int J Mol Sci 25.","DOI":"10.3390\/ijms252312801"},{"key":"2025120510063770000_2024.12.18.629307v2.11","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1097\/TP.0000000000004976","article-title":"The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation","volume":"108","author":"Transplantation Society International BKPCG","year":"2024","journal-title":"Transplantation"},{"key":"2025120510063770000_2024.12.18.629307v2.12","doi-asserted-by":"crossref","unstructured":"Starrett GJ , Yu K , Golubeva Y , Lenz P , Piaskowski ML , Petersen D , Dean M , Israni A , Hernandez BY , Tucker TC , Cheng I , Gonsalves L , Morris CR , Hussain SK , Lynch CF , Harris RS , Prokunina-Olsson L , Meltzer PS , Buck CB , Engels EA . 2023. Evidence for virus-mediated oncogenesis in bladder cancers arising in solid organ transplant recipients. 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Vera Therapeutics Reports Positive Interim Phase 2 Data Showing MAU868 Has Significant BK Antiviral Activity in Kidney Transplant Patients, p 2, https:\/\/www.globenewswire.com\/news-release\/2022\/06\/04\/2456292\/0\/en\/Vera-Therapeutics-Reports-Positive-Interim-Phase-2-Data-Showing-MAU868-Has-Significant-BK-Antiviral-Activity-in-Kidney-Transplant-Patients.html."}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.12.18.629307","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:02:17Z","timestamp":1782277337000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.12.18.629307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,21]]},"references-count":48,"URL":"https:\/\/doi.org\/10.1101\/2024.12.18.629307","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1099\/jgv.0.002197","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,12,21]]},"subtype":"preprint"}}