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Retrospective studies of OMV-based meningococcal vaccines have shown a partial effectiveness against gonorrhea, reigniting hopes for a feasible vaccine. Our study focused on the role of gonococcal lipooligosaccharides (LOS), the most abundant antigens on the surface, in stimulating functional immune responses. By employing detoxified OMV from\n                    <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                    isogenic strains expressing different LOS glycoforms, we observed that antibodies targeting LOS with long \u03b1-chain oligosaccharides correlated with bactericidal activity against a wide range of gonococcal isolates, whereas antibodies that also recognized the \u03b2-chain and consequently the 2C7 epitope could achieve a broader bacterial adhesion-inhibiting effect. The results obtained underscore the potential of targeting defined LOS structures to elicit cross-strain protective immunity. Insights from our findings may guide the design of vaccine strategies to combat the threat posed by antimicrobial-resistant gonorrhea.\n                  <\/jats:p>","DOI":"10.1038\/s41541-025-01271-1","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T11:37:50Z","timestamp":1761824270000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Contribution of the different Neisseria gonorrhoeae lipooligosaccharide structural variants to functional responses elicited by GMMA outer membrane vesicles"],"prefix":"10.1038","volume":"10","author":[{"given":"R.","family":"Cuffaro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Buffi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Romagnoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Giuliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Proietti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Zambelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Spinsanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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