{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T18:51:30Z","timestamp":1781722290791,"version":"3.54.5"},"reference-count":58,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"854","funder":[{"DOI":"10.13039\/100019510","name":"Omeros Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019510","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC","award":["MR\/V032836\/1"],"award-info":[{"award-number":["MR\/V032836\/1"]}]},{"name":"NIHR UK","award":["COV0170"],"award-info":[{"award-number":["COV0170"]}]},{"name":"LifeArc\/CF Trust Innovation Hub","award":["THUB01"],"award-info":[{"award-number":["THUB01"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,6,17]]},"abstract":"<jats:p>\n                    The expanding global crisis of bacterial infections caused by antimicrobial-resistant pathogens has resulted in an urgent need for therapeutics. Previous efforts to target pathogen surface antigens with monoclonal antibodies (mAbs) have sought to activate the complement system, primarily through the antibody-dependent classical pathway. However, most mAbs have induced insufficient complement activation because pathogen evasion strategies disrupt the complex spatiotemporal requirements for activation of the classical pathway initiation complex C1. To address this, we developed a targeted complement activation therapy (T-CAT), which uses antibodies furnished with the enzymatic capability to initiate complement activation directly on the bacterial surface without involvement of the classical pathway initiation complex. We found that T-CAT mAbs directed against bacterial surface antigens can overcome the strategies that pathogens evolved to escape from classical pathway\u2013mediated clearance by the immune system. We further demonstrated that T-CAT mAbs could safely and effectively be used to treat infectious disease in experimental murine models of sepsis and pneumonia caused by\n                    <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Streptococcus pneumoniae<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Neisseria meningitidis<\/jats:italic>\n                    . Together, these data highlight the potential for T-CAT as a next-generation mAb platform with broad applicability against diverse microbial species, including multidrug-resistant pathogens, without promoting drug resistance.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adx4108","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:58:46Z","timestamp":1781719126000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Engineered antibodies bypass bacterial immune evasion to drive complement-mediated protection against lethal infections"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-9848","authenticated-orcid":true,"given":"Youssif M.","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge, Cambridge CB3 0ES, UK."},{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munehisa","family":"Yabuki","sequence":"additional","affiliation":[{"name":"Omeros Corporation, Seattle, WA 98119, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7369-0552","authenticated-orcid":true,"given":"Chanuka H.","family":"Arachchilage","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge, Cambridge CB3 0ES, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Khatri","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge, Cambridge CB3 0ES, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3803-3329","authenticated-orcid":true,"given":"Nicholas J.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge, Cambridge CB3 0ES, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-5386","authenticated-orcid":true,"given":"Sebastian","family":"Bruchmann","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge, Cambridge CB3 0ES, UK."},{"name":"Victor Phillip Dahdaleh Heart &amp; Lung Research Institute, University of Cambridge, Cambridge CB2 0BB, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4597-2471","authenticated-orcid":true,"given":"Aaron","family":"Weimann","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge, Cambridge CB3 0ES, UK."},{"name":"Victor Phillip Dahdaleh Heart &amp; Lung Research Institute, University of Cambridge, Cambridge CB2 0BB, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0387-5318","authenticated-orcid":true,"given":"Karen","family":"Brown","sequence":"additional","affiliation":[{"name":"Victor Phillip Dahdaleh Heart &amp; Lung Research Institute, University of Cambridge, Cambridge CB2 0BB, UK."},{"name":"Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge CB2 0AY, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-5659","authenticated-orcid":true,"given":"Rodrigo Andres","family":"Floto","sequence":"additional","affiliation":[{"name":"Victor Phillip Dahdaleh Heart &amp; Lung Research Institute, University of Cambridge, Cambridge CB2 0BB, UK."},{"name":"Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge CB2 0AY, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-5958","authenticated-orcid":true,"given":"Julian","family":"Parkhill","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge, Cambridge CB3 0ES, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6811-4467","authenticated-orcid":true,"given":"Vidmantas","family":"Petraitis","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3269-8058","authenticated-orcid":true,"given":"Ruta","family":"Petraitiene","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Microbiology &amp; Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA."},{"name":"Center for Innovative Therapeutics and Diagnostics, Richmond, VA 23220, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Briles","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35209, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1649-7563","authenticated-orcid":true,"given":"Larry S.","family":"MacDaniel","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35209, USA."},{"name":"Center for Immunology and Microbial Research, Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Utsugi","sequence":"additional","affiliation":[{"name":"Omeros Corporation, Seattle, WA 98119, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Gragerova","sequence":"additional","affiliation":[{"name":"Omeros Corporation, Seattle, WA 98119, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2538-5989","authenticated-orcid":true,"given":"Ayesha","family":"Misquith","sequence":"additional","affiliation":[{"name":"Omeros Corporation, Seattle, WA 98119, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana","family":"Doulami","sequence":"additional","affiliation":[{"name":"Omeros Corporation, Seattle, WA 98119, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9050-5363","authenticated-orcid":true,"given":"Gregory","family":"Demopulos","sequence":"additional","affiliation":[{"name":"Omeros Corporation, Seattle, WA 98119, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Schwaeble","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge, Cambridge CB3 0ES, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ads3473"},{"key":"e_1_3_2_3_2","first-page":"100561","article-title":"The burden of antimicrobial resistance in the Americas in 2019: A cross-country systematic analysis","volume":"25","author":"Antimicrobial Resistance Collaborators","year":"2023","unstructured":"Antimicrobial Resistance Collaborators, The burden of antimicrobial resistance in the Americas in 2019: A cross-country systematic analysis. Lancet Reg. Health. Am. 25, 100561 (2023).","journal-title":"Lancet Reg. Health. Am."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01867-1"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-019-7796-8"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2022.108233"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2013.08.001"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.933251"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01731-05"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy171"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/1060028017713029"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810603"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1009"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000539"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2018.08.004"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02565-17"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202308-1403OC"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2009.08.006"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2009.139"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz226"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1401011111"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)04004-2"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1086\/376571"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13793"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw021"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2016.08.014"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201085"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00742-18"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012669199"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1080059"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00262"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009655"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2016.06.014"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1328185"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1501049112"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1982.125.5.517"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.279.5.L790"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad758"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/172.1.119"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01358-12"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc06e01s25"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2022.105408"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00589-19"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-143-1-55"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1192767"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2025.126709"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1907833116"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14363-4"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.03.007"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad462"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-015-0782-3"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkae388"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01559-10"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24448-3"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2016.09.007"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2018.04.004"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adi0908"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-91456-0"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adx4108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:59:15Z","timestamp":1781719155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adx4108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":58,"journal-issue":{"issue":"854","published-print":{"date-parts":[[2026,6,17]]}},"alternative-id":["10.1126\/scitranslmed.adx4108"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adx4108","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]},"assertion":[{"value":"2025-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-30","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadx4108"}}