{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T09:37:38Z","timestamp":1794476258233,"version":"4.9.1"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Vaccines"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Gonorrhea, caused by <jats:italic>Neisseria gonorrhoeae<\/jats:italic> (GC) represents a significant public health threat that may be mitigated by an effective vaccine. Vaccines containing <jats:italic>N. meningitidis<\/jats:italic> outer membrane vesicles (OMVs), such as 4CMenB, demonstrated moderate effectiveness in preventing GC infections. Here, we developed NgG, an investigational GC vaccine based on Generalized Modules for Membrane Antigens (GMMA). NgG includes genetically detoxified OMVs from the FA1090 strain, engineered to reduce endotoxin activity and limit immune interference. NgG induced a robust immune response in mice and outperformed the comparator vaccine 4CMenB in several serological and functional tests. Immunization with GMMA from a FA1090 mutant, where major oligosaccharide epitopes are incomplete or absent, revealed that NgG lipooligosaccharide plays a major role in the breadth of functional responses, with protein component also contributing in some GC strains. These results suggest that NgG has the potential to block GC infection through various mechanisms, supporting further vaccine development.<\/jats:p>","DOI":"10.1038\/s41541-025-01190-1","type":"journal-article","created":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T16:59:26Z","timestamp":1751734766000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A novel GMMA-based gonococcal vaccine demonstrates functional immune responses in mice"],"prefix":"10.1038","volume":"10","author":[{"given":"Marco","family":"Spinsanti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Monaci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Romagnoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Buffi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Guido Oreste","family":"Manetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Carboni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Tuscano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia Eleonora","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Tomei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zambelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Cuffaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Taccone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Sammicheli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Gianfaldoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Angiolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Giuliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Marchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Senesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Matano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Pisoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Norais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Romano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Rossi Paccani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Savino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Muzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Fontani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Serruto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Brazzoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Giordano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Fabbrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"D\u2019Oro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oretta","family":"Finco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Immaculada","family":"Margarit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Delany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Bartolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"1190_CR1","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nrmicro.2017.169","volume":"16","author":"SJ Quillin","year":"2018","unstructured":"Quillin, S. J. & Seifert, H. S. Neisseria gonorrhoeae host adaptation and pathogenesis. Nat. Rev. Microbiol. 16, 226\u2013240 (2018).","journal-title":"Nat. Rev. Microbiol."},{"key":"1190_CR2","unstructured":"WHO. Gonorrhoea (Neisseria gonorrhoeae infection). https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/gonorrhoea-(neisseria-gonorrhoeae-infection) (2023)."},{"key":"1190_CR3","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1097\/OLQ.0000000000000592","volume":"44","author":"CL Heumann","year":"2017","unstructured":"Heumann, C. L., Quilter, L. A., Eastment, M. C., Heffron, R. & Hawes, S. E. Adverse birth outcomes and maternal Neisseria gonorrhoeae infection: a population-based cohort study in Washington State. Sex. Transm. Dis. 44, 266\u2013271 (2017).","journal-title":"Sex. Transm. Dis."},{"key":"1190_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1201-9712(98)90087-X","volume":"3","author":"MS Cohen","year":"1998","unstructured":"Cohen, M. S. & Miller, W. C. Sexually transmitted diseases and human immunodeficiency virus infection: cause, effect, or both?. Int. J. Infect. Dis. 3, 1\u20134 (1998).","journal-title":"Int. J. Infect. Dis."},{"key":"1190_CR5","doi-asserted-by":"publisher","first-page":"e627","DOI":"10.1016\/S2666-5247(21)00171-3","volume":"2","author":"M Unemo","year":"2021","unstructured":"Unemo, M. et al. WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017-18: a retrospective observational study. Lancet Microbe 2, e627\u2013e636 (2021).","journal-title":"Lancet Microbe"},{"key":"1190_CR6","unstructured":"Centers for Disease Control and Prevention. Gonorrhea \u2013 CDC Detailed Fact Sheet. https:\/\/www.cdc.gov\/std\/gonorrhea\/stdfact-gonorrhea-detailed.htm (2019)."},{"key":"1190_CR7","unstructured":"World Health organization. Global health sector strategy on Sexually Transmitted Infections, 2016-2021. https:\/\/www.who.int\/publications\/i\/item\/WHO-RHR-16.09 (2016)."},{"key":"1190_CR8","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1097\/QCO.0000000000000992","volume":"37","author":"A Waltmann","year":"2024","unstructured":"Waltmann, A., Chen, J. S. & Duncan, J. A. Promising developments in gonococcal vaccines. Curr. Opin. Infect. Dis. 37, 63\u201369 (2024).","journal-title":"Curr. Opin. Infect. Dis."},{"key":"1190_CR9","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00094-23","volume":"37","author":"E Williams","year":"2024","unstructured":"Williams, E. et al. Neisseria gonorrhoeae vaccines: a contemporary overview. Clin. Microbiol Rev. 37, e0009423 (2024).","journal-title":"Clin. Microbiol Rev."},{"key":"1190_CR10","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.3389\/fimmu.2019.02417","volume":"10","author":"MW Russell","year":"2019","unstructured":"Russell, M. W., Jerse, A. E. & Gray-Owen, S. D. Progress toward a gonococcal vaccine: the way forward. Front. Immunol. 10, 2417 (2019).","journal-title":"Front. Immunol."},{"key":"1190_CR11","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/S1473-3099(21)00754-4","volume":"22","author":"B Wang","year":"2022","unstructured":"Wang, B. et al. Effectiveness and impact of the 4CMenB vaccine against invasive serogroup B meningococcal disease and gonorrhoea in an infant, child, and adolescent programme: an observational cohort and case-control study. Lancet Infect. Dis. 22, 1011\u20131020 (2022).","journal-title":"Lancet Infect. Dis."},{"key":"1190_CR12","first-page":"247","volume":"50","author":"AR Raccagni","year":"2023","unstructured":"Raccagni, A. R. et al. Meningococcus B vaccination effectiveness against Neisseria gonorrhoeae infection in people living with HIV: a case-control study. Sex. Transm. Dis. 50, 247\u2013251 (2023).","journal-title":"Sex. Transm. Dis."},{"key":"1190_CR13","doi-asserted-by":"publisher","first-page":"e1341","DOI":"10.1093\/cid\/ciac436","volume":"76","author":"KJ Bruxvoort","year":"2023","unstructured":"Bruxvoort, K. J. et al. Prevention of Neisseria gonorrhoeae with meningococcal B vaccine: a matched cohort study in Southern California. Clin. Infect. Dis. 76, e1341\u2013e1349 (2023).","journal-title":"Clin. Infect. Dis."},{"key":"1190_CR14","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/S1473-3099(21)00812-4","volume":"22","author":"WE Abara","year":"2022","unstructured":"Abara, W. E. et al. Effectiveness of a serogroup B outer membrane vesicle meningococcal vaccine against gonorrhoea: a retrospective observational study. Lancet Infect. Dis. 22, 1021\u20131029 (2022).","journal-title":"Lancet Infect. Dis."},{"key":"1190_CR15","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.3201\/eid2206.151093","volume":"22","author":"J Whelan","year":"2016","unstructured":"Whelan, J., Klovstad, H., Haugen, I. L., Holle, M. R. & Storsaeter, J. Ecologic study of meningococcal B vaccine and Neisseria gonorrhoeae infection, Norway. Emerg. Infect. Dis. 22, 1137\u20131139 (2016).","journal-title":"Emerg. Infect. Dis."},{"key":"1190_CR16","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1093\/cid\/ciy1061","volume":"69","author":"EA Semchenko","year":"2019","unstructured":"Semchenko, E. A., Tan, A., Borrow, R. & Seib, K. L. The Serogroup B meningococcal vaccine bexsero elicits antibodies to Neisseria gonorrhoeae. Clin. Infect. Dis. 69, 1101\u20131111 (2019).","journal-title":"Clin. Infect. Dis."},{"key":"1190_CR17","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1080\/21645515.2017.1381810","volume":"14","author":"H Petousis-Harris","year":"2018","unstructured":"Petousis-Harris, H. Impact of meningococcal group B OMV vaccines, beyond their brief. Hum. Vaccin Immunother. 14, 1058\u20131063 (2018).","journal-title":"Hum. Vaccin Immunother."},{"key":"1190_CR18","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1080\/21645515.2018.1438028","volume":"14","author":"RF Ochoa-Azze","year":"2018","unstructured":"Ochoa-Azze, R. F. Cross-protection induced by VA-MENGOC-BC(R) vaccine. Hum. Vaccin Immunother. 14, 1064\u20131068 (2018).","journal-title":"Hum. Vaccin Immunother."},{"key":"1190_CR19","doi-asserted-by":"publisher","first-page":"11109","DOI":"10.1073\/pnas.93.20.11109","volume":"93","author":"CR Tinsley","year":"1996","unstructured":"Tinsley, C. R. & Nassif, X. Analysis of the genetic differences between Neisseria meningitidis and Neisseria gonorrhoeae: two closely related bacteria expressing two different pathogenicities. Proc. Natl Acad. Sci. USA 93, 11109\u201311114 (1996).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1190_CR20","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1002\/biot.201400395","volume":"10","author":"L van der Pol","year":"2015","unstructured":"van der Pol, L., Stork, M. & van der Ley, P. Outer membrane vesicles as platform vaccine technology. Biotechnol. J. 10, 1689\u20131706 (2015).","journal-title":"Biotechnol. J."},{"key":"1190_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.715393","volume":"12","author":"F Mancini","year":"2021","unstructured":"Mancini, F. et al. GMMA-based vaccines: the known and the unknown. Front. Immunol. 12, 715393 (2021).","journal-title":"Front. Immunol."},{"key":"1190_CR22","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1080\/14760584.2022.2009803","volume":"21","author":"D Piccioli","year":"2022","unstructured":"Piccioli, D., Bartolini, E. & Micoli, F. GMMA as a \u2018plug and play\u2019 technology to tackle infectious disease to improve global health: context and perspectives for the future. Expert Rev. Vaccines 21, 163\u2013172 (2022).","journal-title":"Expert Rev. Vaccines"},{"key":"1190_CR23","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.vaccine.2016.11.089","volume":"35","author":"G De Benedetto","year":"2017","unstructured":"De Benedetto, G. et al. Characterization of O-antigen delivered by Generalized Modules for Membrane Antigens (GMMA) vaccine candidates against nontyphoidal Salmonella. Vaccine 35, 419\u2013426 (2017).","journal-title":"Vaccine"},{"key":"1190_CR24","doi-asserted-by":"publisher","first-page":"e0134478","DOI":"10.1371\/journal.pone.0134478","volume":"10","author":"C Gerke","year":"2015","unstructured":"Gerke, C. et al. Production of a Shigella sonnei vaccine based on generalized modules for membrane antigens (GMMA), 1790GAHB. PLoS One 10, e0134478 (2015).","journal-title":"PLoS One"},{"key":"1190_CR25","doi-asserted-by":"publisher","first-page":"10428","DOI":"10.1073\/pnas.1807655115","volume":"115","author":"F Micoli","year":"2018","unstructured":"Micoli, F. et al. Comparative immunogenicity and efficacy of equivalent outer membrane vesicle and glycoconjugate vaccines against nontyphoidal Salmonella. Proc. Natl Acad. Sci. USA 115, 10428\u201310433 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1190_CR26","doi-asserted-by":"publisher","first-page":"e072938","DOI":"10.1136\/bmjopen-2023-072938","volume":"13","author":"B Hanumunthadu","year":"2023","unstructured":"Hanumunthadu, B. et al. Salmonella Vaccine Study in Oxford (SALVO) trial: protocol for an observer-participant blind randomised placebo-controlled trial of the iNTS-GMMA vaccine within a European cohort. BMJ Open 13, e072938 (2023).","journal-title":"BMJ Open"},{"key":"1190_CR27","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.ebiom.2017.07.013","volume":"22","author":"O Launay","year":"2017","unstructured":"Launay, O. et al. Safety profile and immunologic responses of a novel vaccine against Shigella sonnei administered intramuscularly, intradermally and intranasally: results from two parallel randomized phase 1 clinical studies in healthy adult volunteers in Europe. EBioMedicine 22, 164\u2013172 (2017).","journal-title":"EBioMedicine"},{"key":"1190_CR28","doi-asserted-by":"publisher","first-page":"335","DOI":"10.3389\/fimmu.2019.00335","volume":"10","author":"O Launay","year":"2019","unstructured":"Launay, O. et al. Booster vaccination with GVGH Shigella sonnei 1790GAHB GMMA vaccine compared to single vaccination in unvaccinated healthy European adults: results from a phase 1 clinical trial. Front. Immunol. 10, 335 (2019).","journal-title":"Front. Immunol."},{"key":"1190_CR29","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1046\/j.1365-2958.2001.02619.x","volume":"42","author":"CD Ellis","year":"2001","unstructured":"Ellis, C. D., Lindner, B., Anjam Khan, C. M., Zahringer, U. & Demarco de Hormaeche, R. The Neisseria gonorrhoeae lpxLII gene encodes for a late-functioning lauroyl acyl transferase, and a null mutation within the gene has a significant effect on the induction of acute inflammatory responses. Mol. Microbiol 42, 167\u2013181 (2001).","journal-title":"Mol. Microbiol"},{"key":"1190_CR30","doi-asserted-by":"publisher","first-page":"3024","DOI":"10.1128\/IAI.00635-16","volume":"84","author":"A Zariri","year":"2016","unstructured":"Zariri, A. et al. Meningococcal outer membrane vesicle composition-dependent activation of the innate immune response. Infect. Immun. 84, 3024\u20133033 (2016).","journal-title":"Infect. Immun."},{"key":"1190_CR31","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1086\/589308","volume":"198","author":"O Koeberling","year":"2008","unstructured":"Koeberling, O., Seubert, A. & Granoff, D. M. Bactericidal antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed factor H-binding protein and genetically attenuated endotoxin. J. Infect. Dis. 198, 262\u2013270 (2008).","journal-title":"J. Infect. Dis."},{"key":"1190_CR32","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1177\/1753425916684201","volume":"23","author":"M Hellum","year":"2017","unstructured":"Hellum, M. et al. The Neisseria meningitidis lpxL1 mutant induces less tissue factor expression and activity in primary human monocytes and monocyte-derived microvesicles than the wild type meningococcus. Innate Immun. 23, 196\u2013205 (2017).","journal-title":"Innate Immun."},{"key":"1190_CR33","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1093\/infdis\/jiv024","volume":"212","author":"S Gulati","year":"2015","unstructured":"Gulati, S. et al. Antibody to reduction modifiable protein increases the bacterial burden and the duration of gonococcal infection in a mouse model. J. Infect. Dis. 212, 311\u2013315 (2015).","journal-title":"J. Infect. Dis."},{"key":"1190_CR34","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1084\/jem.164.5.1735","volume":"164","author":"PA Rice","year":"1986","unstructured":"Rice, P. A., Vayo, H. E., Tam, M. R. & Blake, M. S. Immunoglobulin G antibodies directed against protein III block killing of serum-resistant Neisseria gonorrhoeae by immune serum. J. Exp. Med. 164, 1735\u20131748 (1986).","journal-title":"J. Exp. Med."},{"key":"1190_CR35","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1080\/21645515.2015.1027467","volume":"11","author":"M Santone","year":"2015","unstructured":"Santone, M. et al. A new TLR2 agonist promotes cross-presentation by mouse and human antigen presenting cells. Hum. Vaccin Immunother. 11, 2038\u20132050 (2015).","journal-title":"Hum. Vaccin Immunother."},{"key":"1190_CR36","doi-asserted-by":"publisher","first-page":"24922","DOI":"10.1074\/jbc.M114.566570","volume":"289","author":"O Rossi","year":"2014","unstructured":"Rossi, O. et al. Modulation of endotoxicity of Shigella generalized modules for membrane antigens (GMMA) by genetic lipid A modifications: relative activation of TLR4 and TLR2 pathways in different mutants. J. Biol. Chem. 289, 24922\u201324935 (2014).","journal-title":"J. Biol. Chem."},{"key":"1190_CR37","doi-asserted-by":"publisher","first-page":"3754","DOI":"10.1016\/j.vaccine.2018.10.082","volume":"37","author":"S Valentini","year":"2019","unstructured":"Valentini, S. et al. Monocyte-activation test to reliably measure the pyrogenic content of a vaccine: An in vitro pyrogen test to overcome in vivo limitations. Vaccine 37, 3754\u20133760 (2019).","journal-title":"Vaccine"},{"key":"1190_CR38","doi-asserted-by":"publisher","first-page":"3187","DOI":"10.3389\/fimmu.2018.03187","volume":"9","author":"A Lovett","year":"2018","unstructured":"Lovett, A. & Duncan, J. A. Human immune responses and the natural history of Neisseria gonorrhoeae Infection. Front. Immunol. 9, 3187 (2018).","journal-title":"Front. Immunol."},{"key":"1190_CR39","doi-asserted-by":"publisher","first-page":"3416","DOI":"10.4049\/jimmunol.1102746","volume":"188","author":"S Gulati","year":"2012","unstructured":"Gulati, S., Agarwal, S., Vasudhev, S., Rice, P. A. & Ram, S. Properdin is critical for antibody-dependent bactericidal activity against Neisseria gonorrhoeae that recruit C4b-binding protein. J. Immunol. 188, 3416\u20133425 (2012).","journal-title":"J. Immunol."},{"key":"1190_CR40","doi-asserted-by":"publisher","first-page":"3902","DOI":"10.4049\/jimmunol.141.11.3902","volume":"141","author":"P Densen","year":"1988","unstructured":"Densen, P., McRill, C. M. & Ross, S. C. Assembly of the membrane attack complex promotes decay of the alternative pathway C3 convertase on Neisseria gonorrhoeae. J. Immunol. 141, 3902\u20133909 (1988).","journal-title":"J. Immunol."},{"key":"1190_CR41","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1097\/00007435-200110000-00001","volume":"28","author":"KA Schmidt","year":"2001","unstructured":"Schmidt, K. A. et al. Experimental gonococcal urethritis and reinfection with homologous gonococci in male volunteers. Sex. Transm. Dis. 28, 555\u2013564 (2001).","journal-title":"Sex. Transm. Dis."},{"key":"1190_CR42","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.micpath.2017.06.035","volume":"110","author":"Z Zeng","year":"2017","unstructured":"Zeng, Z. et al. lgtF effects of Haemophilus parasuis LOS induced inflammation through regulation of NF-kappaB and MAPKs signaling pathways. Micro. Pathog. 110, 380\u2013384 (2017).","journal-title":"Micro. Pathog."},{"key":"1190_CR43","doi-asserted-by":"publisher","first-page":"3352","DOI":"10.1128\/IAI.68.6.3352-3361.2000","volume":"68","author":"MJ Filiatrault","year":"2000","unstructured":"Filiatrault, M. J. et al. Construction and characterization of Haemophilus ducreyi lipooligosaccharide (LOS) mutants defective in expression of heptosyltransferase III and beta1,4-glucosyltransferase: identification of LOS glycoforms containing lactosamine repeats. Infect. Immun. 68, 3352\u20133361 (2000).","journal-title":"Infect. Immun."},{"key":"1190_CR44","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1099\/mic.0.26912-0","volume":"150","author":"DW Hood","year":"2004","unstructured":"Hood, D. W. et al. Three genes, lgtF, lic2C and lpsA, have a primary role in determining the pattern of oligosaccharide extension from the inner core of Haemophilus influenzae LPS. Microbiology150, 2089\u20132097 (2004).","journal-title":"Microbiology"},{"key":"1190_CR45","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1093\/infdis\/174.6.1223","volume":"174","author":"S Gulati","year":"1996","unstructured":"Gulati, S., McQuillen, D. P., Mandrell, R. E., Jani, D. B. & Rice, P. A. Immunogenicity of Neisseria gonorrhoeae lipooligosaccharide epitope 2C7, widely expressed in vivo with no immunochemical similarity to human glycosphingolipids. J. Infect. Dis. 174, 1223\u20131237 (1996).","journal-title":"J. Infect. Dis."},{"key":"1190_CR46","doi-asserted-by":"publisher","first-page":"e1003559","DOI":"10.1371\/journal.ppat.1003559","volume":"9","author":"S Gulati","year":"2013","unstructured":"Gulati, S. et al. Immunization against a saccharide epitope accelerates clearance of experimental gonococcal infection. PLoS Pathog. 9, e1003559 (2013).","journal-title":"PLoS Pathog."},{"key":"1190_CR47","doi-asserted-by":"crossref","unstructured":"Fiorino, F. et al. Long-term anti-bacterial immunity against systemic infection by Salmonella enterica serovar typhimurium elicited by a GMMA-based vaccine. Vaccines 9, 495 (2021).","DOI":"10.3390\/vaccines9050495"},{"key":"1190_CR48","doi-asserted-by":"crossref","unstructured":"Gulati, S. et al. Preclinical efficacy of a lipooligosaccharide peptide mimic candidate gonococcal vaccine. mBio 10, e02552-19 (2019).","DOI":"10.1128\/mBio.02552-19"},{"key":"1190_CR49","doi-asserted-by":"crossref","unstructured":"Ruiz Garcia, Y. et al. Urgent need to understand and prevent gonococcal infection: from the laboratory to real-world context. J. Infect. Dis. 230, e758\u2013e767 (2024).","DOI":"10.1093\/infdis\/jiae289"},{"key":"1190_CR50","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1016\/j.vaccine.2010.12.039","volume":"29","author":"PB Keiser","year":"2011","unstructured":"Keiser, P. B. et al. A phase 1 study of a meningococcal native outer membrane vesicle vaccine made from a group B strain with deleted lpxL1 and synX, over-expressed factor H binding protein, two PorAs and stabilized OpcA expression. Vaccine 29, 1413\u20131420 (2011).","journal-title":"Vaccine"},{"key":"1190_CR51","doi-asserted-by":"publisher","first-page":"e90525","DOI":"10.1371\/journal.pone.0090525","volume":"9","author":"G Li","year":"2014","unstructured":"Li, G. et al. Antibodies with higher bactericidal activity induced by a Neisseria gonorrhoeae Rmp deletion mutant strain. PLoS One 9, e90525 (2014).","journal-title":"PLoS One"},{"key":"1190_CR52","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1172\/JCI116190","volume":"91","author":"FA Plummer","year":"1993","unstructured":"Plummer, F. A. et al. Antibody to Rmp (outer membrane protein 3) increases susceptibility to gonococcal infection. J. Clin. Invest. 91, 339\u2013343 (1993).","journal-title":"J. Clin. Invest."},{"key":"1190_CR53","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1099\/mic.0.000227","volume":"162","author":"S Maharjan","year":"2016","unstructured":"Maharjan, S. et al. Dissection of the function of the RmpM periplasmic protein from Neisseria meningitidis. Microbiology 162, 364\u2013375 (2016).","journal-title":"Microbiology"},{"key":"1190_CR54","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00388-22","volume":"8","author":"Y Liu","year":"2023","unstructured":"Liu, Y. et al. 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. mSphere 8, e0038822 (2023).","journal-title":"mSphere"},{"key":"1190_CR55","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1038\/mi.2017.11","volume":"10","author":"Y Liu","year":"2017","unstructured":"Liu, Y. et al. Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model. Mucosal. Immunol. 10, 1594\u20131608 (2017).","journal-title":"Mucosal. Immunol."},{"key":"1190_CR56","doi-asserted-by":"publisher","first-page":"e1008602","DOI":"10.1371\/journal.ppat.1008602","volume":"16","author":"I Leduc","year":"2020","unstructured":"Leduc, I. et al. The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae. PLoS Pathog. 16, e1008602 (2020).","journal-title":"PLoS Pathog."},{"key":"1190_CR57","doi-asserted-by":"publisher","first-page":"3937","DOI":"10.1128\/IAI.67.8.3937-3946.1999","volume":"67","author":"SR Hedges","year":"1999","unstructured":"Hedges, S. R., Mayo, M. S., Mestecky, J., Hook, E. W. 3rd & Russell, M. W. Limited local and systemic antibody responses to Neisseria gonorrhoeae during uncomplicated genital infections. Infect. Immun. 67, 3937\u20133946 (1999).","journal-title":"Infect. Immun."},{"key":"1190_CR58","doi-asserted-by":"publisher","first-page":"1248613","DOI":"10.3389\/fimmu.2023.1248613","volume":"14","author":"T Belcher","year":"2023","unstructured":"Belcher, T., Rollier, C. S., Dold, C., Ross, J. D. C. & MacLennan, C. A. Immune responses to Neisseria gonorrhoeae and implications for vaccine development. Front. Immunol. 14, 1248613 (2023).","journal-title":"Front. Immunol."},{"key":"1190_CR59","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3389\/fmicb.2011.00052","volume":"2","author":"Y Liu","year":"2011","unstructured":"Liu, Y., Feinen, B. & Russell, M. W. New concepts in immunity to Neisseria gonorrhoeae: innate responses and suppression of adaptive immunity favor the pathogen, not the host. Front. Microbiol. 2, 52 (2011).","journal-title":"Front. Microbiol."},{"key":"1190_CR60","doi-asserted-by":"publisher","first-page":"683","DOI":"10.3389\/fimmu.2019.00683","volume":"10","author":"H Petousis-Harris","year":"2019","unstructured":"Petousis-Harris, H. & Radcliff, F. J. Exploitation of Neisseria meningitidis Group B OMV vaccines against N. gonorrhoeae to inform the development and deployment of effective gonorrhea vaccines. Front. Immunol. 10, 683 (2019).","journal-title":"Front. Immunol."},{"key":"1190_CR61","doi-asserted-by":"publisher","first-page":"e00095","DOI":"10.1128\/mBio.00095-11","volume":"2","author":"Y Liu","year":"2011","unstructured":"Liu, Y. & Russell, M. W. Diversion of the immune response to Neisseria gonorrhoeae from Th17 to Th1\/Th2 by treatment with anti-transforming growth factor beta antibody generates immunological memory and protective immunity. mBio 2, e00095\u201300011 (2011).","journal-title":"mBio"},{"key":"1190_CR62","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/mi.2013.36","volume":"7","author":"Y Liu","year":"2014","unstructured":"Liu, Y., Liu, W. & Russell, M. W. Suppression of host adaptive immune responses by Neisseria gonorrhoeae: role of interleukin 10 and type 1 regulatory T cells. Mucosal. Immunol. 7, 165\u2013176 (2014).","journal-title":"Mucosal. Immunol."},{"key":"1190_CR63","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1126\/science.451601","volume":"205","author":"A Nicholson","year":"1979","unstructured":"Nicholson, A. & Lepow, I. H. Host defense against Neisseria meningitidis requires a complement-dependent bactericidal activity. Science 205, 298\u2013299 (1979).","journal-title":"Science"},{"key":"1190_CR64","doi-asserted-by":"publisher","first-page":"e3000323","DOI":"10.1371\/journal.pbio.3000323","volume":"17","author":"S Gulati","year":"2019","unstructured":"Gulati, S. et al. Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody. PLoS Biol. 17, e3000323 (2019).","journal-title":"PLoS Biol."},{"key":"1190_CR65","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1093\/infdis\/jiab630","volume":"225","author":"LA Lewis","year":"2022","unstructured":"Lewis, L. A. et al. Efficacy of an experimental gonococcal lipooligosaccharide mimitope vaccine requires terminal complement. J. Infect. Dis. 225, 1861\u20131864 (2022).","journal-title":"J. Infect. Dis."},{"key":"1190_CR66","doi-asserted-by":"crossref","unstructured":"Ram, S. et al. Gonococcal lipooligosaccharide sialylation: virulence factor and target for novel immunotherapeutics. Pathog. Dis. 75, ftx049 (2017).","DOI":"10.1093\/femspd\/ftx049"},{"key":"1190_CR67","doi-asserted-by":"publisher","first-page":"1119834","DOI":"10.3389\/fmicb.2023.1119834","volume":"14","author":"E Walker","year":"2023","unstructured":"Walker, E., van Niekerk, S., Hanning, K., Kelton, W. & Hicks, J. Mechanisms of host manipulation by Neisseria gonorrhoeae. Front. Microbiol. 14, 1119834 (2023).","journal-title":"Front. Microbiol."},{"key":"1190_CR68","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/0264-410X(85)90003-9","volume":"3","author":"EC Tramont","year":"1985","unstructured":"Tramont, E. C. & Boslego, J. W. Pilus vaccines. Vaccine 3, 3\u201310 (1985).","journal-title":"Vaccine"},{"key":"1190_CR69","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1128\/CMR.17.4.965-981.2004","volume":"17","author":"JL Edwards","year":"2004","unstructured":"Edwards, J. L. & Apicella, M. A. The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin. Microbiol. Rev. 17, 965\u2013981 (2004).","journal-title":"Clin. Microbiol. Rev."},{"key":"1190_CR70","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1046\/j.1365-2958.2001.02666.x","volume":"42","author":"HA Harvey","year":"2001","unstructured":"Harvey, H. A., Jennings, M. P., Campbell, C. A., Williams, R. & Apicella, M. A. Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor. Mol. Microbiol. 42, 659\u2013672 (2001).","journal-title":"Mol. Microbiol."},{"key":"1190_CR71","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1111\/j.1574-6976.2010.00260.x","volume":"35","author":"M Sadarangani","year":"2011","unstructured":"Sadarangani, M., Pollard, A. J. & Gray-Owen, S. D. Opa proteins and CEACAMs: pathways of immune engagement for pathogenic Neisseria. FEMS Microbiol. Rev. 35, 498\u2013514 (2011).","journal-title":"FEMS Microbiol. Rev."},{"key":"1190_CR72","doi-asserted-by":"crossref","unstructured":"Brooks, G. F. & Lammel, C. J. Humoral immune response to gonococcal infections. Clin. Microbiol. Rev. 2, S5\u2013S10 (1989).","DOI":"10.1128\/CMR.2.Suppl.S5"},{"key":"1190_CR73","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1128\/iai.43.2.706-709.1984","volume":"43","author":"EW Hook 3rd","year":"1984","unstructured":"Hook, E. W. 3rd, Olsen, D. A. & Buchanan, T. M. Analysis of the antigen specificity of the human serum immunoglobulin G immune response to complicated gonococcal infection. Infect. Immun. 43, 706\u2013709 (1984).","journal-title":"Infect. Immun."},{"key":"1190_CR74","doi-asserted-by":"crossref","unstructured":"Ram, S. et al. A novel sialylation site on Neisseria gonorrhoeae lipooligosaccharide links heptose II lactose expression with pathogenicity. Infect. Immun. 86, e00285-18 (2018).","DOI":"10.1128\/IAI.00285-18"},{"key":"1190_CR75","doi-asserted-by":"publisher","first-page":"321","DOI":"10.3389\/fimmu.2019.00321","volume":"10","author":"S Gulati","year":"2019","unstructured":"Gulati, S., Shaughnessy, J., Ram, S. & Rice, P. A. Targeting lipooligosaccharide (LOS) for a gonococcal vaccine. Front. Immunol. 10, 321 (2019).","journal-title":"Front. Immunol."},{"key":"1190_CR76","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1128\/iai.32.2.641-648.1981","volume":"32","author":"I Nachamkin","year":"1981","unstructured":"Nachamkin, I., Cannon, J. G. & Mittler, R. S. Monoclonal antibodies against Neisseria gonorrhoeae: production of antibodies directed against a strain-specific cell surface antigen. Infect. Immun. 32, 641\u2013648 (1981).","journal-title":"Infect. Immun."},{"key":"1190_CR77","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1128\/CVI.00542-10","volume":"18","author":"O Koeberling","year":"2011","unstructured":"Koeberling, O., Delany, I. & Granoff, D. M. A critical threshold of meningococcal factor H binding protein expression is required for increased breadth of protective antibodies elicited by native outer membrane vesicle vaccines. Clin. Vaccin. Immunol. 18, 736\u2013742 (2011).","journal-title":"Clin. Vaccin. Immunol."},{"key":"1190_CR78","doi-asserted-by":"publisher","first-page":"e47039","DOI":"10.1371\/journal.pone.0047039","volume":"7","author":"F Micoli","year":"2012","unstructured":"Micoli, F. et al. O:2-CRM(197) conjugates against Salmonella Paratyphi A. PLoS One 7, e47039 (2012).","journal-title":"PLoS One"},{"key":"1190_CR79","doi-asserted-by":"publisher","first-page":"36550","DOI":"10.1074\/jbc.274.51.36550","volume":"274","author":"R Yamasaki","year":"1999","unstructured":"Yamasaki, R. et al. Structural and immunochemical characterization of a Neisseria gonorrhoeae epitope defined by a monoclonal antibody 2C7; the antibody recognizes a conserved epitope on specific lipo-oligosaccharides in spite of the presence of human carbohydrate epitopes. J. Biol. Chem. 274, 36550\u201336558 (1999).","journal-title":"J. Biol. Chem."},{"key":"1190_CR80","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/laban.1219","volume":"46","author":"EM Weber","year":"2017","unstructured":"Weber, E. M., Dallaire, J. A., Gaskill, B. N., Pritchett-Corning, K. R. & Garner, J. P. Aggression in group-housed laboratory mice: why can\u2019t we solve the problem?. Lab. Anim.46, 157\u2013161 (2017).","journal-title":"Lab. Anim."}],"container-title":["npj Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41541-025-01190-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-025-01190-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-025-01190-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T18:03:02Z","timestamp":1751738582000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41541-025-01190-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,5]]},"references-count":80,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1190"],"URL":"https:\/\/doi.org\/10.1038\/s41541-025-01190-1","relation":{},"ISSN":["2059-0105"],"issn-type":[{"value":"2059-0105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,5]]},"assertion":[{"value":"13 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors are, or were at the time of the study, employees of the GSK group of companies and may own shares in GSK and\/or be inventor(s) on patent owned by GSK.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"146"}}