{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T02:17:34Z","timestamp":1768011454519,"version":"3.49.0"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.14859.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000}}],"reference-count":60,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["087622"],"award-info":[{"award-number":["087622"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["109031"],"award-info":[{"award-number":["109031"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p><ns4:bold>Background:<\/ns4:bold>Protein-conjugate capsular polysaccharide vaccines can potentially control invasive meningococcal disease (IMD) caused by five (A, C, W, X, Y) of the six IMD-associated serogroups.\u00a0 Concerns raised by immunological similarity of the serogroup B capsule to human neural cell carbohydrates, meant that \u2018serogroup B substitute\u2019 vaccines target more variable subcapsular protein antigens.\u00a0 A successful approach using outer membrane vesicles (OMVs) as major vaccine components had limited strain coverage. In 4CMenB (Bexsero<ns4:sup>\u00ae<\/ns4:sup>), recombinant proteins have been added to ameliorate this problem.\u00a0<\/ns4:p><ns4:p><ns4:bold>Methods:<\/ns4:bold>\u00a0Scalable, portable, genomic techniques were used to investigate the Bexsero<ns4:sup>\u00ae<\/ns4:sup>OMV protein diversity in meningococcal populations. Shotgun proteomics identified 461 proteins in the OMV, defining a complex proteome. Amino acid sequences for the 24 proteins most likely to be involved in cross-protective immune responses were catalogued within the<ns4:ext-link xmlns:ns3=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" ns3:href=\"https:\/\/pubmlst.org\/neisseria\/\">PubMLST.org\/neisseria<\/ns4:ext-link>database using a novel OMV peptide Typing (OMVT) scheme.<\/ns4:p><ns4:p><ns4:bold>Results:<\/ns4:bold>Among these proteins there was variation in the extent of diversity and association with meningococcal lineages, identified as clonal complexes (ccs), ranging from the most conserved peptides (FbpA, NEISp0578, and putative periplasmic protein, NEISp1063) to the most diverse (TbpA, NEISp1690). \u00a0There were 1752 unique OMVTs identified amongst 2492\/3506 isolates examined by whole-genome sequencing (WGS). These OMVTs were grouped into clusters (sharing \u226518 identical OMVT peptides), with 45.3% of isolates assigned to one of 27 OMVT clusters. OMVTs and OMVT clusters were strongly associated with cc, genogroup, and Bexsero<ns4:sup>\u00ae<\/ns4:sup>antigen variants, demonstrating that combinations of OMV proteins exist in discrete, non-overlapping combinations associated with genogroup and Bexsero<ns4:sup>\u00ae<\/ns4:sup>Antigen Sequence Type. This highly structured population of IMD-associated meningococci is consistent with strain structure models invoking host immune and\/or metabolic selection.<\/ns4:p><ns4:p><ns4:bold>Conclusions:<\/ns4:bold><ns4:bold\/>The OMVT scheme facilitates region-specific WGS investigation of meningococcal diversity and is an open-access, portable tool with applications for vaccine development, especially in the choice of antigen combinations, assessment and implementation.<\/ns4:p>","DOI":"10.12688\/wellcomeopenres.14859.2","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T07:56:16Z","timestamp":1552982176000},"page":"151","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Typing complex meningococcal vaccines to understand diversity and population structure of key vaccine antigens"],"prefix":"10.12688","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0942-3707","authenticated-orcid":false,"given":"Charlene M. 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The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}