{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T03:45:50Z","timestamp":1779939950462,"version":"3.53.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the ZonMW-Vici","award":["09150181910001"],"award-info":[{"award-number":["09150181910001"]}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NWO-Vici"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bacterial infections represent a substantial global health challenge, impacting both human and veterinary health. The ongoing evolution of antibiotic-resistant pathogens, coupled with limited new antibiotic discoveries, urges the need for alternative strategies to treat and prevent these infections. Passive immunization with monoclonal antibodies (mAbs) is gaining interest as a promising alternative. Here, we report an experimental pipeline for generating human mAbs from healthy donor B cells using synthetic mimics of complex bacterial glycans. We identified functional mAbs recognizing discrete and unique epitopes on the surface glycans of two bacterial priority pathogens; Staphylococcus aureus and Streptococcus pyogenes. The use of chemically-defined synthetic glycans was critical for the discovery and systematic characterization of mAbs. From a heterogeneous mix of B cell specificities, antibody sequences were identified, leading to the production of mAbs with distinct reactivities against immunodominant but also to less common or even masked epitopes. The pipeline can be adapted to different glycan targets, donor material or specific antibody isotypes. This work thereby paves the way for the discovery of glycan-specific mAbs with clinical relevance to treat, prevent or diagnose infections with S. aureus, S. pyogenes or other bacterial pathogens.<\/jats:p>","DOI":"10.1093\/glycob\/cwaf064","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:14:46Z","timestamp":1760105686000},"source":"Crossref","is-referenced-by-count":1,"title":["Editor\u2019s Choice Platform for identifying human glycan-specific antibodies against bacterial pathogens using synthetic glycan fragments"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4104-0522","authenticated-orcid":false,"given":"A Robin","family":"Temming","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam ,","place":["the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious diseases , Meibergdreef 9 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Claireaux","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam ,","place":["the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious diseases , Meibergdreef 9 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gius","family":"Kerster","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam ,","place":["the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious diseases , Meibergdreef 9 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvie E","family":"Groenewege","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thijs","family":"Voskuilen","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry, Leiden University , Einsteinweg 55 2333 CC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry, Leiden University , Einsteinweg 55 2333 CC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen D C","family":"Cod\u00e9e","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry, Leiden University , Einsteinweg 55 2333 CC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit J","family":"van Gils","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam ,","place":["the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious diseases , Meibergdreef 9 1105 AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2695-5863","authenticated-orcid":false,"given":"Nina M","family":"van Sorge","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam ,","place":["the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious diseases , Meibergdreef 9 1105 AZ Amsterdam ,","place":["The Netherlands"]},{"name":"Netherlands Reference Laboratory for Bacterial Meningitis , Amsterdam UMC location AMC, Meibergdreef 9, 1105 AZ Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"2025110901140245200_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00118-5","volume-title":"Lancet Infect Dis","author":"WHO","year":"2025"},{"key":"2025110901140245200_ref2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9070717","article-title":"Influenza a virus hemagglutinin trimer, head and stem proteins identify and quantify different hemagglutinin-specific b cell subsets in humans","volume":"9","author":"Aartse","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"2025110901140245200_ref3","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41541-023-00730-x","article-title":"Update on the development of group a streptococcus vaccines","volume":"8","author":"Ajay Castro","year":"2023","journal-title":"NPJ Vaccines"},{"key":"2025110901140245200_ref4","doi-asserted-by":"publisher","first-page":"10461","DOI":"10.1002\/chem.202101242","article-title":"(automated) synthesis of well-defined staphylococcus aureus wall teichoic acid fragments","volume":"27","author":"Ali","year":"2021","journal-title":"Chemistry."},{"key":"2025110901140245200_ref5","first-page":"114","article-title":"Specificity of persistence of antibody to the streptococcal group a carbohydrate in rheumatic valvular heart disease","volume":"105","author":"Appleton","year":"1985","journal-title":"J Lab Clin Med"},{"key":"2025110901140245200_ref6","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1182\/blood-2006-06-015461","article-title":"Staphylococcal superantigen-like 5 binds psgl-1 and inhibits p-selectin-mediated neutrophil rolling","volume":"109","author":"Bestebroer","year":"2007","journal-title":"Blood."},{"key":"2025110901140245200_ref7","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc5902","article-title":"Potent neutralizing antibodies from covid-19 patients define multiple targets of vulnerability","volume-title":"Science","author":"Brouwer"},{"key":"2025110901140245200_ref8","doi-asserted-by":"publisher","first-page":"18909","DOI":"10.1073\/pnas.1209126109","article-title":"Methicillin resistance in staphylococcus aureus requires glycosylated wall teichoic acids","volume":"109","author":"Brown","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025110901140245200_ref9","article-title":"Anti-wall teichoic antibodies and conjugates","author":"Brown","year":"2015"},{"key":"2025110901140245200_ref10","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/S1473-3099(05)70267-X","article-title":"The global burden of group a streptococcal diseases","volume":"5","author":"Carapetis","year":"2005","journal-title":"Lancet Infect Dis"},{"key":"2025110901140245200_ref11","doi-asserted-by":"publisher","first-page":"4539","DOI":"10.1038\/s41467-022-32232-0","article-title":"A public antibody class recognizes an s2 epitope exposed on open conformations of sars-cov-2 spike","volume":"13","author":"Claireaux","year":"2022","journal-title":"Nat Commun"},{"key":"2025110901140245200_ref12","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1038\/s41586-019-1416-8","article-title":"Do not discard staphylococcus aureus wta as a vaccine antigen","volume":"572","author":"Dalen","year":"2019","journal-title":"Nature."},{"key":"2025110901140245200_ref13","doi-asserted-by":"publisher","first-page":"43039","DOI":"10.1038\/srep43039","article-title":"Group a streptococcal m1 protein provides resistance against the antimicrobial activity of histones","volume":"7","author":"Dohrmann","year":"2017","journal-title":"Sci Rep"},{"key":"2025110901140245200_ref14","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41589-019-0251-4","article-title":"Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides","volume":"15","author":"Edgar","year":"2019","journal-title":"Nat Chem Biol"},{"key":"2025110901140245200_ref15","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1172\/JCI7132","article-title":"Cytotoxic mab from rheumatic carditis recognizes heart valves and laminin","volume":"106","author":"Galvin","year":"2000","journal-title":"J Clin Invest"},{"key":"2025110901140245200_ref16","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050","volume":"404","author":"GBD 2021 Antimicrobial Resistance Collaborators","year":"2024","journal-title":"Lancet."},{"key":"2025110901140245200_ref17","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/s41586-018-0730-x","article-title":"Methicillin-resistant staphylococcus aureus alters cell wall glycosylation to evade immunity","volume":"563","author":"Gerlach","year":"2018","journal-title":"Nature."},{"key":"2025110901140245200_ref18","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1038\/219866a0","article-title":"Isolation from heart valves of glycopeptides which share immunological properties with streptococcus haemolyticus group a polysaccharides","volume":"219","author":"Goldstein","year":"1968","journal-title":"Nature."},{"key":"2025110901140245200_ref19","first-page":"105424","article-title":"Identifying who global priority endemic pathogens for vaccine research and development (r&d) using multi-criteria decision analysis (mcda): an objective of the immunization agenda 2030","volume":"110","author":"Hasso-Agopsowicz","year":"2024","journal-title":"E Bio Medicine"},{"key":"2025110901140245200_ref20","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2024.29.47.2400212","article-title":"Expert consensus on antimicrobial resistance research priorities to focus development and implementation of antibacterial vaccines and monoclonal antibodies","volume":"29","author":"Hassoun-Kheir","year":"2024","journal-title":"Euro Surveill"},{"key":"2025110901140245200_ref21","doi-asserted-by":"publisher","first-page":"101734","DOI":"10.1016\/j.xcrm.2024.101734","article-title":"Glycan-specific igm is critical for human immunity to staphylococcus aureus","volume":"5","author":"Hendriks","year":"2024","journal-title":"Cell Rep Med"},{"key":"2025110901140245200_ref22","doi-asserted-by":"publisher","first-page":"4951","DOI":"10.4049\/jimmunol.1201294","article-title":"Specific serum ig recognizing staphylococcal wall teichoic acid induces complement-mediated opsonophagocytosis against staphylococcus aureus","volume":"189","author":"Jung","year":"2012","journal-title":"J Immunol"},{"key":"2025110901140245200_ref23","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/nm892","article-title":"Mimicry and autoantibody-mediated neuronal cell signaling in sydenham chorea","volume":"9","author":"Kirvan","year":"2003","journal-title":"Nat Med"},{"key":"2025110901140245200_ref24","doi-asserted-by":"publisher","first-page":"30956","DOI":"10.1074\/jbc.M113.509893","article-title":"Glycoepitopes of staphylococcal wall teichoic acid govern complement-mediated opsonophagocytosis via human serum antibody and mannose-binding lectin","volume":"288","author":"Kurokawa","year":"2013","journal-title":"J Biol Chem"},{"key":"2025110901140245200_ref25","doi-asserted-by":"publisher","first-page":"4247","DOI":"10.1128\/IAI.00767-15","article-title":"Surface glycopolymers are crucial for in vitro anti-wall teichoic acid igg-mediated complement activation and opsonophagocytosis of staphylococcus aureus","volume":"83","author":"Lee","year":"2015","journal-title":"Infect Immun"},{"key":"2025110901140245200_ref26","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/nature16057","article-title":"Novel antibody-antibiotic conjugate eliminates intracellular s","volume":"527","author":"Lehar","year":"2015","journal-title":"Nature"},{"key":"2025110901140245200_ref27","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.15.618486","article-title":"Human anti-glycan reactivity is driven by the selection of b cells utilizing private antibody gene rearrangements that are affinity maturated in germinal","volume-title":"bioRxiv: the preprint server for biology","author":"New","year":"2024"},{"key":"2025110901140245200_ref28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/82_2012_280","article-title":"Group a streptococcal diseases and their global burden","volume":"368","author":"Ralph","year":"2013","journal-title":"Curr Top Microbiol Immunol"},{"key":"2025110901140245200_ref29","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.diagmicrobio.2013.02.020","article-title":"Microbiology of skin and soft tissue infections in the age of community-acquired methicillin-resistant staphylococcus aureus","volume":"76","author":"Ray","year":"2013","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2025110901140245200_ref30","doi-asserted-by":"publisher","first-page":"19441","DOI":"10.1074\/jbc.M117.815910","article-title":"The molecular mechanism of n-acetylglucosamine side-chain attachment to the lancefield group a carbohydrate in streptococcus pyogenes","volume":"292","author":"Rush","year":"2017","journal-title":"J Biol Chem"},{"key":"2025110901140245200_ref31","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.3389\/fimmu.2019.01296","article-title":"Conceptual approaches to modulating antibody effector functions and circulation half-life","volume":"10","author":"Saunders","year":"2019","journal-title":"Front Immunol"},{"key":"2025110901140245200_ref32","doi-asserted-by":"publisher","first-page":"3788","DOI":"10.1128\/JB.01452-09","article-title":"Synthetic effects of secg and secy2 mutations on exoproteome biogenesis in staphylococcus aureus","volume":"192","author":"Sibbald","year":"2010","journal-title":"J Bacteriol"},{"key":"2025110901140245200_ref33","doi-asserted-by":"publisher","DOI":"10.3390\/antib8020030","article-title":"The ligands for human igg and their effector functions","volume":"8","author":"Taeye","year":"2019","journal-title":"Antibodies (Basel)"},{"key":"2025110901140245200_ref34","doi-asserted-by":"publisher","first-page":"e69739","DOI":"10.1371\/journal.pone.0069739","article-title":"Intradermal immunization with wall teichoic acid (wta) elicits and augments an anti-wta igg response that protects mice from methicillin-resistant staphylococcus aureus infection independent of mannose-binding lectin status","volume":"8","author":"Takahashi","year":"2013","journal-title":"PLoS One"},{"key":"2025110901140245200_ref35","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management","volume":"28","author":"Tong","year":"2015","journal-title":"Clin Microbiol Rev"},{"key":"2025110901140245200_ref36","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41541-023-00609-x","article-title":"The streptococcus pyogenes vaccine landscape","volume":"8","author":"Walkinshaw","year":"2023","journal-title":"NPJ Vaccines"},{"key":"2025110901140245200_ref37","volume-title":"Chemical synthesis of fragments of streptococcal cell wall polysaccharides","author":"Wang","year":"2020"},{"key":"2025110901140245200_ref38","doi-asserted-by":"publisher","first-page":"13405","DOI":"10.1074\/jbc.M109.096172","article-title":"Glycosylation of wall teichoic acid in staphylococcus aureus by tarm","volume":"285","author":"Xia","year":"2010","journal-title":"J Biol Chem"}],"container-title":["Glycobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/glycob\/advance-article-pdf\/doi\/10.1093\/glycob\/cwaf064\/64612909\/cwaf064.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/glycob\/article-pdf\/35\/11\/cwaf064\/64612909\/cwaf064.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/glycob\/article-pdf\/35\/11\/cwaf064\/64612909\/cwaf064.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T06:14:08Z","timestamp":1762668848000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/glycob\/article\/doi\/10.1093\/glycob\/cwaf064\/8280425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":38,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11,6]]}},"URL":"https:\/\/doi.org\/10.1093\/glycob\/cwaf064","relation":{},"ISSN":["1460-2423"],"issn-type":[{"value":"1460-2423","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,10,10]]},"article-number":"cwaf064"}}