{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:55:04Z","timestamp":1785412504921,"version":"3.56.0"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["108876\/B\/15\/Z"],"award-info":[{"award-number":["108876\/B\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["214374\/Z\/18\/Z"],"award-info":[{"award-number":["214374\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,3,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Excessive binding of antibodies to the bacterial cell surface can paradoxically increase resistance of some Gram-negative pathogens to complement-mediated killing (CMK). We examined the CMK of 336\n                      <jats:italic toggle=\"yes\">Neisseria gonorrhoeae<\/jats:italic>\n                      isolates from 283 participants recruited to a clinical trial. Serum bactericidal assays revealed 3% (9\/283) of the autologous participant sera blocked CMK. Gonococci isolated from these participants were resistant to the autologous host serum, but sensitive to pooled healthy control sera (HCS) and protected by autologous host serum in a 1:1 mixture with HCS. Analysis of clinical metadata showed that there was a significantly higher proportion of blocking sera found in participants with urethral infection and from men within the transmission network of men who have sex with women, when compared to the whole cohort. Following antibody purification from participants with blocking sera (5\/9), total IgG protected autologous isolates from HCS-mediated killing. A closer examination of IgG subclasses using whole gonococcal cell ELISAs revealed a significant correlation between increased IgG2 binding and decreased IgG3 binding to the cell surface of isolates that were resistant to CMK. This indicates that IgG2 prevents bactericidal IgG3 from initiating CMK, with an increased IgG2:IgG3 ratio blocking CMK of gonococci. We therefore reveal a previously unrecognized mechanism by which blocking antibodies prevent CMK of\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The antigenic variation of\n                      <jats:italic toggle=\"yes\">Neisseria gonorrhoeae<\/jats:italic>\n                      and a limited mechanistic understanding of immune responses to this bacterium have presented multiple challenges to generating a protective vaccine. Here, we use a collection of\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      clinical isolates (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 336) for a robust analysis of the host immune response to infection. We reveal a mechanism for serum resistance in which some isolates of\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      drive the production of inhibitory IgG2 antibodies, which block the activity of IgG3 bactericidal antibodies. Importantly, an increased ratio of IgG2:IgG3 bound to the bacterium promotes serum resistance. Recently, there has been increased interest in developing a vaccine against\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      given the observation that the licensed outer membrane vesicle-based vaccine against\n                      <jats:italic toggle=\"yes\">Neisseria meningitidis<\/jats:italic>\n                      (MeNZB) generated some cross-protection against\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      . Thus, the mechanism described here should guide the development of a vaccine that simultaneously prevents serum resistance and promotes serum killing of the gonococcus.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03367-23","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:00:33Z","timestamp":1769781633000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of\n                    <i>Neisseria gonorrhoeae<\/i>\n                    complement-mediated killing during acute gonorrhea is dependent upon the IgG2:IgG3 antibody ratio"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-7422","authenticated-orcid":false,"given":"Samantha A.","family":"McKeand","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03angcq70","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Microbiology and Infection, University of Birmingham","place":["Birmingham, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Sir William Dunn School of Pathology, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian E.","family":"Faustini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03angcq70","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Immunology and Immunotherapy, College of Medicine and Health, University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Cook","sequence":"additional","affiliation":[{"name":"The Binding Site","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki","family":"Kennett","sequence":"additional","affiliation":[{"name":"The Binding Site","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Drayson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03angcq70","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Immunology and Immunotherapy, College of Medicine and Health, University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0248-964X","authenticated-orcid":true,"given":"Adam F.","family":"Cunningham","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03angcq70","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Immunology and Immunotherapy, College of Medicine and Health, University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9954-4977","authenticated-orcid":true,"given":"Ian R.","family":"Henderson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Molecular Bioscience, University of Queensland","place":["St. Lucia, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8366-3245","authenticated-orcid":true,"given":"Christoph M.","family":"Tang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Sir William Dunn School of Pathology, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D. C.","family":"Ross","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00635kd98","id-type":"ROR","asserted-by":"publisher"}],"name":"Sexual Health and HIV, University Hospitals Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Cole","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03angcq70","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Microbiology and Infection, University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8567-7998","authenticated-orcid":true,"given":"Amanda E.","family":"Rossiter-Pearson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03angcq70","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Microbiology and Infection, University of Birmingham","place":["Birmingham, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/03angcq70","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"WHO. 2024. 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Immunological mechanisms of Neisseria gonorrhoeae infection: an update. Zhonghua Nan Ke Xue 24:452\u2013456.","journal-title":"Zhonghua Nan Ke Xue"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03367-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03367-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:04:22Z","timestamp":1773234262000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.03367-23"}},"subtitle":[],"editor":[{"given":"Marvin","family":"Whiteley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,11]]}},"alternative-id":["10.1128\/mbio.03367-23"],"URL":"https:\/\/doi.org\/10.1128\/mbio.03367-23","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]},"assertion":[{"value":"2023-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03367-23"}}