{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:02:03Z","timestamp":1793325723165,"version":"4.5.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"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>Background<\/jats:title><jats:p><jats:italic>Neisseria gonorrhoeae<\/jats:italic>, causative agent of the human sexually transmitted infection gonorrhea, is a significant global health concern because of increasing antimicrobial resistance and the lack of an effective vaccine. Recent ecological analyses have shown a reduced incidence of gonorrhea in recipients of detergent-extracted outer membrane vesicle (OMV)-containing meningococcal vaccine, which has contributed to identification of shared, protective antigens. Previously, our group has developed an immunobioinformatics-based pipeline (CASS, Candidate Antigen Selection Strategy) for identification of gonococcal hypothetical proteins expressed during human natural mucosal infections, as novel vaccine candidates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we expanded the immunological characterization of three targets, NGO0690, NGO0948 and Csp (copper storage protein, previously called NGO1701) to include analysis of their efficacy in a mouse model of gonococcal vaginal infection when combined as a trivalent subunit vaccine and adjuvanted with Alum and MPLA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We reported induction of systemic and mucosal antibody responses, serum bactericidal activity against heterologous <jats:italic>N. gonorrhoeae<\/jats:italic> strains, and accelerated bacterial clearance in vivo. Immune profiling revealed a balanced Th1\/Th2 response, based on IgG antibody subclasses and cytokines. Antigen dose de-escalation experiments in female and male mice showed sustained antibody production against the individual antigens and against whole bacteria. The latter were slightly lower than with the original dose vaccine particularly in male mice, who also exhibited a distinct cytokine pattern and weaker complement-mediated serum bactericidal activity (SBA) titers compared to female mice. These findings underscore the importance of considering sex-based differences in vaccine evaluation. A bivalent vaccine containing only NGO0690 and Csp was still protective <jats:italic>in vivo<\/jats:italic>, supporting the value of multivalent approaches to address gonococcal antigenic diversity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Overall, our results suggested that the rational design of our multi-antigen subunit vaccines holds translational potential for enhancing broadly protective immune responses and protection against <jats:italic>N. gonorrhoeae<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1688536","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T05:30:17Z","timestamp":1758519017000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Preclinical in vivo evaluation of a gonococcal multivalent vaccine containing antigens identified by CASS"],"prefix":"10.3389","volume":"16","author":[{"given":"Shea K.","family":"Roe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Gulati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Genco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Massari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"B1","unstructured":"Sexually transmitted disease surveillance\n          \n          \n          \n          2023"},{"key":"B2","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/s41572-019-0128-6","article-title":"Gonorrhoea","volume":"5","author":"Unemo","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03187","article-title":"Human immune responses and the natural history of Neisseria gonorrhoeae infection","volume":"9","author":"Lovett","year":"2018","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/sextrans-2023-055977","article-title":"Higher Neisseria gonorrhoeae bacterial load in coinfections with Chlamydia trachomatis compared with Neisseria gonorrhoeae single infections does not lead to more symptoms","volume":"100","author":"van Dessel","year":"2024","journal-title":"Sex Transm Infect"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac408","article-title":"Neisseria gonorrhoeae infection in women increases with rising gonococcal burdens in partners: chlamydia coinfection in women increases gonococcal burden","volume":"226","author":"Su","year":"2022","journal-title":"J Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1097\/00002030-199301000-00015","article-title":"Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study","volume":"7","author":"Laga","year":"1993","journal-title":"AIDS"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)02190-9","article-title":"Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. 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