{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:19:43Z","timestamp":1785406783627,"version":"3.56.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["214374\/A\/18\/Z"],"award-info":[{"award-number":["214374\/A\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Vaccines targeting\n                      <jats:italic toggle=\"yes\">Neisseria gonorrhoeae<\/jats:italic>\n                      are needed to\n                        reduce disease burden and help address the problem of antimicrobial\n                        resistance, with an understanding of relationships between gonococcal\n                        genetics and molecules influencing diversity, infection, and the immune\n                        response essential for developing effective vaccine formulations.\n                        Whole-genome sequence data can be used to investigate these relationships\n                        among thousands of gonococcal isolates, allowing the study of antigenic\n                        diversity on a population scale. Such analyses typically examine antigenic\n                        diversity occurring in complete protein sequences, generating mean diversity\n                        indices and phylogenetic analyses that can inform on vaccine potential;\n                        however, to detect and measure the immune responses elicited, epitope\n                        characterization within an antigen helps guide vaccine formulations, with\n                        epitopes commonly located in surface-exposed regions of a protein. Here, we\n                        analyzed the genetic diversity of the major gonococcal antigen, PorB, in WGS\n                        from 22,227\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">gonorrhoeae<\/jats:italic>\n                      isolates. We\n                        characterized the diversity of all eight surface-exposed outer membrane\n                        loops, or variable regions (VRs), and generated a PorB VR subtyping scheme\n                        to facilitate the global and temporal detection of circulating PorB\n                        subtypes. These analyses identified the presence of dominant VR combinations\n                        that persisted over time, indicative of (i) epistatic interactions between\n                        VRs and (ii) positive selection. Strain-specific, anti-PorB IgG responses\n                        directed toward distinct VR subtypes were detected in sera obtained from\n                        participants vaccinated with 4CMenB. The deconstruction of PorB into each\n                        surface-exposed loop provides a powerful approach for evaluating vaccine\n                        candidates: the methods used here allow immunodominant regions to be\n                        detected, which is invaluable for further vaccine investigations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      In the context of rising global gonorrhea cases, the development of vaccines\n                        becomes a priority; however,\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      antigenic\n                        diversity and its ability to evade the immune system complicate vaccine\n                        development. This study characterizes the genetic diversity of the outer\n                        membrane protein, PorB, a key component of the outer membrane and a major\n                        gonococcal antigen. Using genomics and machine-learning techniques, this\n                        research identified dominant PorB variants that drive the immune response,\n                        proposing potential vaccine candidates and improving our understanding of\n                        the evolutionary forces maintaining genome structure and biological fitness.\n                        Understanding these processes is crucial for designing vaccines that\n                        effectively target\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      and combat the spread of\n                        multidrug-resistant gonococci.\n                    <\/jats:p>\n                  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