{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:01:53Z","timestamp":1793325713989,"version":"4.5.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Limited protective immunologic responses to natural <jats:italic>N. gonorrhoeae<\/jats:italic> infection and a lack of knowledge about mechanisms of protection have hampered development of an effective vaccine. Recent studies in humans and mice have found meningococcal outer membrane vesicle-containing vaccines (OMV) induce cross species immune responses against gonococci and are associated with protection. The exact mechanisms or how humoral and cellular immunity are related to protection, remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To study this, we immunized mice with two meningococcal OMV-containing vaccines known to accelerate clearance of <jats:italic>N. gonorrhoeae<\/jats:italic>, 4CMenB and OMV from an engineered <jats:italic>N. meningitidis<\/jats:italic> strain lacking major surface antigens PorA, PorB, and Rmp (MC58 \u0394ABR). We assessed serologic and cellular immune signatures associated with these immunizations and assessed bacterial clearance in the mice using a vaginal\/cervical gonococcal infection model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mice immunized with 4CMenB or MC58 \u0394ABR demonstrated shortened courses of recovery of vaginal <jats:italic>N. gonorrhoeae<\/jats:italic> compared to control mice immunized with alum alone. Vaccination with 4CMenB or MC58\u0394ABR OMV elicited serum and vaginal cross-reactive anti-Ng-OMV antibody responses that were augmented after vaginal challenge with <jats:italic>N. gonorrhoeae<\/jats:italic>. Further, splenocytes in 4CMenB and MC58 \u0394ABR immunized mice exhibited elevated cytokine production after restimulation with heterologous <jats:italic>N. gonorrhoeae<\/jats:italic> OMV when compared to splenocytes from Alum immunized mice. We further tested for correlations between bacterial burden and the measured anti-gonococcal immune responses within each vaccination group and found different immunologic parameters associated with reduced bacterial burden for each vaccine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings suggest the cross-protection against gonococcal infection induced by different meningococcal OMV vaccines is likely multifactorial and mediated by different humoral and cellular immune responses induced by these two vaccines.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1539795","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T01:14:28Z","timestamp":1744334068000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Protection against N. gonorrhoeae induced by OMV-based meningococcal vaccines are associated with cross-species directed humoral and cellular immune responses"],"prefix":"10.3389","volume":"16","author":[{"given":"Weiyan","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Waltmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marguerite B.","family":"Little","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristie L.","family":"Connolly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn A.","family":"Matthias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keena S.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary 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