{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:40:08Z","timestamp":1789080008056,"version":"build-2803163510"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["221924\/Z\/20\/Z"],"award-info":[{"award-number":["221924\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fell Oxford University Press Research Fund","award":["214374\/Z\/18\/Z"],"award-info":[{"award-number":["214374\/Z\/18\/Z"]}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["U19 AI189178"],"award-info":[{"award-number":["U19 AI189178"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neisseria gonorrhoeae is a major sexually transmitted pathogen with rising antimicrobial resistance. Epidemiological studies suggest meningococcal outer membrane vesicle (OMV) vaccines, eg 4CMenB (Bexsero), offer partial cross-protection, but immune correlates remain undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using a murine genital tract infection model, we compared systemic and mucosal responses after immunization with Bexsero, gonococcal OMVs (Ng OMVs) with alum, or alum alone. Vaccinated mice were challenged intravaginally with N. gonorrhoeae. Serum bactericidal activity (SBA) was measured, and antigen-specific IgG responses were profiled using gonococcal protein microarrays. Murine responses were compared with high-risk Bexsero-immunized humans and patients with gonococcal infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bexsero significantly accelerated bacterial clearance compared with Ng OMV or alum. Serum and vaginal IgG profiles were highly correlated, revealing distinct antigenic signatures between groups. Bexsero elicited responses to gonococcal orthologs of its recombinant antigens (GNA1030, GNA2091, NHBA), whereas Ng OMVs induced Opa, PilQ, and MtrE responses. SBA did not correlate with clearance; however, early PMN influx was associated with reduced bacterial load. Antigen-specific IgG patterns were concordant between Bexsero-immunized mice and humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Protein microarrays with multivariate analysis identified antibody signatures associated with protection, supporting the translational value of this model for defining correlates of protection and guiding gonococcal vaccine development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag216","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:23:00Z","timestamp":1777468980000},"page":"e1443-e1453","source":"Crossref","is-referenced-by-count":1,"title":["Investigation of Correlates of Protection Against Gonococcal Infection by Comparative Immunoprofiling of Responses in Experimental and Clinical Studies"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-7422","authenticated-orcid":false,"given":"Samantha A","family":"McKeand","sequence":"first","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8215-0843","authenticated-orcid":false,"given":"Fidel Ramirez","family":"Bencomo","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester , Manchester ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Soc","sequence":"additional","affiliation":[{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah A","family":"Jones","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Thistlethwaite","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester , Manchester ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4579-5190","authenticated-orcid":false,"given":"Zhenyi","family":"Gu","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice","family":"Nduati","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Hospital Road , Kilifi ,","place":["Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard J","family":"Sanders","sequence":"additional","affiliation":[{"name":"The Aurum Institute , Johannesburg, Gauteng ,","place":["Republic of South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5118-3172","authenticated-orcid":false,"given":"Ann E","family":"Jerse","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University , Bethesda, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4350-5354","authenticated-orcid":false,"given":"Jeremy P","family":"Derrick","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester , Manchester ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8366-3245","authenticated-orcid":false,"given":"Christoph M","family":"Tang","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"2026061615215466700_jiag216-B1","author":"WHO"},{"key":"2026061615215466700_jiag216-B2","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1093\/cid\/ciz145","article-title":"Risk of ectopic pregnancy and tubal infertility following gonorrhea and chlamydia infections","volume":"69","author":"Reekie","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2026061615215466700_jiag216-B3","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/infdis\/161.3.531","article-title":"Maternal gonococcal infection as a preventable risk factor for low birth weight","volume":"161","author":"Elliott","year":"1990","journal-title":"J Infect Dis"},{"key":"2026061615215466700_jiag216-B4","first-page":"471","article-title":"Epidemiology and control of gonococcal ophthalmia neonatorum","volume":"67","author":"Laga","year":"1989","journal-title":"Bull World Health Organ"},{"key":"2026061615215466700_jiag216-B5","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"2026061615215466700_jiag216-B6","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/S0140-6736(17)31449-6","article-title":"Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: a retrospective case-control study","volume":"390","author":"Petousis-Harris","year":"2017","journal-title":"Lancet"},{"key":"2026061615215466700_jiag216-B7","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jinf.2023.05.021","article-title":"4CMenB sustained vaccine effectiveness against invasive meningococcal B disease and gonorrhoea at three years post programme implementation","volume":"87","author":"Wang","year":"2023","journal-title":"J Infect"},{"key":"2026061615215466700_jiag216-B8","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/OLQ.0000000000001771","article-title":"Meningococcus B vaccination effectiveness against Neisseria gonorrhoeae infection in people living with HIV: a case-control study","volume":"50","author":"Raccagni","year":"2023","journal-title":"Sex Transm Dis"},{"key":"2026061615215466700_jiag216-B9","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1016\/j.vaccine.2005.01.063","article-title":"MeNZB: a safe and highly immunogenic tailor-made vaccine against the New Zealand Neisseria meningitidis serogroup B disease epidemic strain","volume":"23","author":"Oster","year":"2005","journal-title":"Vaccine"},{"key":"2026061615215466700_jiag216-B10","author":"Rappuoli R, Pizza M, Masignani V, Vadivelu K."},{"key":"2026061615215466700_jiag216-B11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003528","article-title":"Distinct binding and immunogenic properties of the gonococcal homologue of meningococcal factor h binding protein","volume":"9","author":"Jongerius","year":"2013","journal-title":"PLoS Pathog"},{"key":"2026061615215466700_jiag216-B12","doi-asserted-by":"crossref","first-page":"6712","DOI":"10.1038\/s41467-024-51053-x","article-title":"Profiling IgG and IgA antibody responses during vaccination and infection in a high-risk gonorrhoea population","volume":"15","author":"Stejskal","year":"2024","journal-title":"Nat Commun"},{"key":"2026061615215466700_jiag216-B13","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41541-024-01018-4","article-title":"NHBA antibodies elicited by 4CMenB vaccination are key for serum bactericidal activity against Neisseria gonorrhoeae","volume":"9","author":"Tzeng","year":"2024","journal-title":"NPJ Vaccines"},{"key":"2026061615215466700_jiag216-B14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1008602","article-title":"The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae","volume":"16","author":"Leduc","year":"2020","journal-title":"PLoS Pathog"},{"key":"2026061615215466700_jiag216-B15","doi-asserted-by":"crossref","DOI":"10.1128\/msphere.00940-24","article-title":"Meningococcal vaccine 4CMenB elicits a robust cellular immune response that targets but is not consistently protective against Neisseria gonorrhoeae during murine vaginal infection","volume":"10","author":"Zeppa","year":"2025","journal-title":"mSphere"},{"key":"2026061615215466700_jiag216-B16","doi-asserted-by":"crossref","first-page":"1539795","DOI":"10.3389\/fimmu.2025.1539795","article-title":"Protection against N. gonorrhoeae induced by OMV-based meningococcal vaccines are associated with cross-species directed humoral and cellular immune responses","volume":"16","author":"Zhu","year":"2025","journal-title":"Front Immunol"},{"key":"2026061615215466700_jiag216-B17","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fmicb.2011.00124","article-title":"Vaccines for gonorrhea: can we rise to the challenge?","volume":"2","author":"Zhu","year":"2011","journal-title":"Front Microbiol"},{"key":"2026061615215466700_jiag216-B18","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1038\/mi.2017.11","article-title":"Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model","volume":"10","author":"Liu","year":"2017","journal-title":"Mucosal Immunol"},{"key":"2026061615215466700_jiag216-B19","doi-asserted-by":"crossref","DOI":"10.1128\/msphere.00388-22","article-title":"Microencapsulated IL-12 drives genital tract immune responses to intranasal gonococcal outer membrane vesicle vaccine and induces resistance to vaginal infection with diverse strains of Neisseria gonorrhoeae","volume":"8","author":"Liu","year":"2023","journal-title":"mSphere"},{"key":"2026061615215466700_jiag216-B20","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.tim.2023.10.002","article-title":"Gonococcal PorB: a multifaceted modulator of host immune responses","volume":"32","author":"Jones","year":"2024","journal-title":"Trends Microbiol"},{"key":"2026061615215466700_jiag216-B21","doi-asserted-by":"crossref","DOI":"10.1128\/cmr.00094-23","article-title":"Neisseria gonorrhoeae vaccines: a contemporary overview","volume":"37","author":"Williams","year":"2024","journal-title":"Clin Microbiol Rev"},{"key":"2026061615215466700_jiag216-B22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1012688","article-title":"Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design","volume":"20","author":"Jones","year":"2024","journal-title":"PLoS Pathog"},{"key":"2026061615215466700_jiag216-B23","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.1128\/IAI.67.11.5699-5708.1999","article-title":"Experimental gonococcal genital tract infection and opacity protein expression in estradiol-treated mice","volume":"67","author":"Jerse","year":"1999","journal-title":"Infect Immun"},{"key":"2026061615215466700_jiag216-B24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package","volume":"28","author":"Kuhn","year":"2008","journal-title":"J Stat Softw"},{"issue":"(7","key":"2026061615215466700_jiag216-B25","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1099\/00221287-143-7-2127","article-title":"Involvement of the gonococcal MtrE protein in the resistance of Neisseria gonorrhoeae to toxic hydrophobic agents","volume":"143","author":"Delahay","year":"1997","journal-title":"Microbiology (Reading)"},{"key":"2026061615215466700_jiag216-B26","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1128\/JB.01833-06","article-title":"Pilq Missense mutations have diverse effects on PilQ multimer formation, piliation, and pilus function in Neisseria gonorrhoeae","volume":"189","author":"Helm","year":"2007","journal-title":"J Bacteriol"},{"key":"2026061615215466700_jiag216-B27","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1128\/iai.21.2.575-584.1978","article-title":"Studies on gonococcus infection. XV. Identification of surface proteins of Neisseria gonorrhoeae correlated with leukocyte association","volume":"21","author":"King","year":"1978","journal-title":"Infect Immun"},{"key":"2026061615215466700_jiag216-B28","doi-asserted-by":"crossref","first-page":"9938","DOI":"10.1021\/ja503093y","article-title":"Structure of the Neisserial outer membrane protein Opa(6)(0): loop flexibility essential to receptor recognition and bacterial engulfment","volume":"136","author":"Fox","year":"2014","journal-title":"J Am Chem Soc"},{"key":"2026061615215466700_jiag216-B29","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1172\/JCI112167","article-title":"Mechanism of action of blocking immunoglobulin G for Neisseria gonorrhoeae","volume":"76","author":"Joiner","year":"1985","journal-title":"J Clin Invest"},{"key":"2026061615215466700_jiag216-B30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nrmicro.2017.169","article-title":"Neisseria gonorrhoeae host adaptation and pathogenesis","volume":"16","author":"Quillin","year":"2018","journal-title":"Nat Rev Microbiol"},{"key":"2026061615215466700_jiag216-B31","first-page":"1054","article-title":"The biology of Neisseria adhesins","volume":"2","author":"Hung","year":"2013","journal-title":"Biology (Basel)"},{"key":"2026061615215466700_jiag216-B32","doi-asserted-by":"crossref","first-page":"1350344","DOI":"10.3389\/fimmu.2024.1350344","article-title":"Neisseria gonorrhoeae lipooligosaccharide glycan epitopes recognized by bactericidal IgG antibodies elicited by the meningococcal group B-directed vaccine, MenB-4C","volume":"15","author":"Tzeng","year":"2024","journal-title":"Front Immunol"},{"key":"2026061615215466700_jiag216-B33","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1146\/annurev-immunol-031210-101317","article-title":"Immunoglobulin responses at the mucosal interface","volume":"29","author":"Cerutti","year":"2011","journal-title":"Annu Rev Immunol"},{"key":"2026061615215466700_jiag216-B34","doi-asserted-by":"crossref","first-page":"4388","DOI":"10.1073\/pnas.1012861108","article-title":"Transfer of IgG in the female genital tract by MHC class I-related neonatal fc receptor (FcRn) confers protective immunity to vaginal infection","volume":"108","author":"Li","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026061615215466700_jiag216-B35","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s41577-019-0261-1","article-title":"Rethinking mucosal antibody responses: IgM, IgG and IgD join IgA","volume":"20","author":"Chen","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"2026061615215466700_jiag216-B36","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1093\/infdis\/jiab630","article-title":"Efficacy of an experimental gonococcal lipooligosaccharide mimitope vaccine requires terminal complement","volume":"225","author":"Lewis","year":"2022","journal-title":"J Infect Dis"},{"key":"2026061615215466700_jiag216-B37","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.02500-23","article-title":"Preclinical efficacy of a cell division protein candidate gonococcal vaccine identified by artificial intelligence","volume":"14","author":"Gulati","year":"2023","journal-title":"mBio"},{"key":"2026061615215466700_jiag216-B38","doi-asserted-by":"crossref","first-page":"1565862","DOI":"10.3389\/fimmu.2025.1565862","article-title":"Isolation of human monoclonal antibodies from 4CMenB vaccinees reveals PorB and LOS as the main OMV components inducing cross-strain protection","volume":"16","author":"Vezzani","year":"2025","journal-title":"Front Immunol"},{"key":"2026061615215466700_jiag216-B39","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1093\/cid\/ciy821","article-title":"The effect of influenza virus on the human oropharyngeal microbiome","volume":"68","author":"Ramos-Sevillano","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2026061615215466700_jiag216-B40","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1099\/mic.0.000227","article-title":"Dissection of the function of the RmpM periplasmic protein from Neisseria meningitidis","volume":"162","author":"Maharjan","year":"2016","journal-title":"Microbiology (Reading)"},{"key":"2026061615215466700_jiag216-B41","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1111\/j.1462-5822.2008.01205.x","article-title":"Neisseria gonorrhoeae suppresses the oxidative burst of human polymorphonuclear leukocytes","volume":"10","author":"Criss","year":"2008","journal-title":"Cell Microbiol"},{"key":"2026061615215466700_jiag216-B42","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1111\/j.1462-5822.2009.01308.x","article-title":"Resistance of Neisseria gonorrhoeae to non-oxidative killing by adherent human polymorphonuclear leucocytes","volume":"11","author":"Criss","year":"2009","journal-title":"Cell Microbiol"},{"key":"2026061615215466700_jiag216-B43","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.mib.2014.11.006","article-title":"Neisseria meningitidis: pathogenesis and immunity","volume":"23","author":"Pizza","year":"2015","journal-title":"Curr Opin Microbiol"},{"key":"2026061615215466700_jiag216-B44","author":"UK Health Security Agency"},{"key":"2026061615215466700_jiag216-B45","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/S1473-3099(24)00236-6","article-title":"Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2(2 factorial design","volume":"24","author":"Molina","year":"2024","journal-title":"Lancet Infect Dis"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiag216\/68185731\/jiag216.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/233\/6\/e1443\/68185731\/jiag216.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/233\/6\/e1443\/68185731\/jiag216.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:22:09Z","timestamp":1781637729000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/233\/6\/e1443\/8664755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":45,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,4,29]]},"published-print":{"date-parts":[[2026,6,16]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiag216","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6,15]]},"published":{"date-parts":[[2026,4,29]]}}}