{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T11:45:11Z","timestamp":1792755911340,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1008602","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000}}],"reference-count":95,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AAI14024"],"award-info":[{"award-number":["AAI14024"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009898","name":"Defense Health Agency","doi-asserted-by":"crossref","award":["IHBISP_18_017"],"award-info":[{"award-number":["IHBISP_18_017"]}],"id":[{"id":"10.13039\/100009898","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UC6-AI058607"],"award-info":[{"award-number":["UC6-AI058607"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI007273-33"],"award-info":[{"award-number":["T32AI007273-33"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19-AI144180"],"award-info":[{"award-number":["U19-AI144180"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance in\n                    <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                    (\n                    <jats:italic>Ng<\/jats:italic>\n                    ). Current gonorrhea vaccine research is in the stages of antigen discovery and the identification of protective immune responses, and no vaccine has been tested in clinical trials in over 30 years. Recently, however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup B\n                    <jats:italic>Neisseria meningitidis<\/jats:italic>\n                    (\n                    <jats:italic>Nm<\/jats:italic>\n                    ) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea. Here we directly tested the hypothesis that\n                    <jats:italic>Nm<\/jats:italic>\n                    OMVs induce cross-protection against gonorrhea in a well-characterized female mouse model of\n                    <jats:italic>Ng<\/jats:italic>\n                    genital tract infection. We found that immunization with the licensed\n                    <jats:italic>Nm<\/jats:italic>\n                    OMV-based vaccine 4CMenB (Bexsero) significantly accelerated clearance and reduced the\n                    <jats:italic>Ng<\/jats:italic>\n                    bacterial burden compared to administration of alum or PBS. Serum IgG and vaginal IgA and IgG that cross-reacted with\n                    <jats:italic>Ng<\/jats:italic>\n                    OMVs were induced by 4CMenB vaccination by either the subcutaneous or intraperitoneal routes. Antibodies from vaccinated mice recognized several\n                    <jats:italic>Ng<\/jats:italic>\n                    surface proteins, including PilQ, BamA, MtrE, NHBA (known to be recognized by humans), PorB, and Opa. Immune sera from both mice and humans recognized\n                    <jats:italic>Ng<\/jats:italic>\n                    PilQ and several proteins of similar apparent molecular weight, but MtrE was only recognized by mouse serum. Pooled sera from 4CMenB-immunized mice showed a 4-fold increase in serum bactericidal\n                    <jats:sub>50<\/jats:sub>\n                    titers against the challenge strain; in contrast, no significant difference in bactericidal activity was detected when sera from 4CMenB-immunized and unimmunized subjects were compared. Our findings directly support epidemiological evidence that\n                    <jats:italic>Nm<\/jats:italic>\n                    OMVs confer cross-species protection against gonorrhea, and implicate several\n                    <jats:italic>Ng<\/jats:italic>\n                    surface antigens as potentially protective targets. Additionally, this study further defines the usefulness of murine infection model as a relevant experimental system for gonorrhea vaccine development.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1008602","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T16:45:01Z","timestamp":1607445901000},"page":"e1008602","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":111,"title":["The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae"],"prefix":"10.1371","volume":"16","author":[{"given":"Isabelle","family":"Leduc","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7516-4427","authenticated-orcid":true,"given":"Kristie L.","family":"Connolly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afrin","family":"Begum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knashka","family":"Underwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0984-5144","authenticated-orcid":true,"given":"Stephen","family":"Darnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-8777","authenticated-orcid":true,"given":"William M.","family":"Shafer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9799-0001","authenticated-orcid":true,"given":"Jacqueline T.","family":"Balthazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew N.","family":"Macintyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0391-6594","authenticated-orcid":true,"given":"Gregory D.","family":"Sempowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4438-2018","authenticated-orcid":true,"given":"Joseph A.","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9796-9162","authenticated-orcid":true,"given":"Marguerite B.","family":"Little","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazia","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1238-7228","authenticated-orcid":true,"given":"Eric C.","family":"Garges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann E.","family":"Jerse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,8]]},"reference":[{"issue":"8","key":"ppat.1008602.ref001","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016","volume":"97","author":"J Rowley","year":"2019","journal-title":"Bull World Health 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regulatory T cells","volume":"7","author":"Y Liu","year":"2014","journal-title":"Mucosal immunology"},{"issue":"28","key":"ppat.1008602.ref024","doi-asserted-by":"crossref","first-page":"11218","DOI":"10.1074\/jbc.RA117.001209","article-title":"Properly folded and functional PorB from Neisseria gonorrhoeae inhibits dendritic cell stimulation of CD4(+) T cell proliferation","volume":"293","author":"W Zhu","year":"2018","journal-title":"J Biol Chem"},{"issue":"7","key":"ppat.1008602.ref025","doi-asserted-by":"crossref","first-page":"e41260","DOI":"10.1371\/journal.pone.0041260","article-title":"Neisseria gonorrhoeae suppresses dendritic cell-induced, antigen-dependent CD4 T cell proliferation","volume":"7","author":"W Zhu","year":"2012","journal-title":"PloS one"},{"key":"ppat.1008602.ref026","article-title":"Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: a retrospective case-control study","author":"H Petousis-Harris","year":"2017","journal-title":"Lancet"},{"issue":"5","key":"ppat.1008602.ref027","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1080\/21645515.2017.1381810","article-title":"Impact of meningococcal group B OMV vaccines, beyond their brief","volume":"14","author":"H Petousis-Harris","year":"2018","journal-title":"Human vaccines & immunotherapeutics"},{"issue":"Suppl 2","key":"ppat.1008602.ref028","doi-asserted-by":"crossref","first-page":"B87","DOI":"10.1016\/j.vaccine.2012.01.033","article-title":"The new multicomponent vaccine against meningococcal serogroup B, 4CMenB: immunological, functional and structural characterization of the antigens","volume":"30","author":"D Serruto","year":"2012","journal-title":"Vaccine"},{"issue":"9","key":"ppat.1008602.ref029","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1111\/j.1600-0463.2012.02903.x","article-title":"Novel meningococcal 4CMenB vaccine antigens\u2014prevalence and polymorphisms of the encoding 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Packiam","year":"2012","journal-title":"Mucosal immunology"},{"key":"ppat.1008602.ref058","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fmicb.2011.00107","article-title":"Estradiol-treated female mice as surrogate hosts for Neisseria gonorrhoeae genital tract infections","volume":"2","author":"AE Jerse","year":"2011","journal-title":"Frontiers in microbiology"},{"issue":"6","key":"ppat.1008602.ref059","doi-asserted-by":"crossref","first-page":"e00892","DOI":"10.1128\/mBio.00892-13","article-title":"Lipid A\u2019s structure mediates Neisseria gonorrhoeae fitness during experimental infection of mice and men","volume":"4","author":"MM Hobbs","year":"2013","journal-title":"mBio"},{"issue":"6","key":"ppat.1008602.ref060","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1038\/mi.2017.11","article-title":"Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model","volume":"10","author":"Y Liu","year":"2017","journal-title":"Mucosal immunology"},{"issue":"11","key":"ppat.1008602.ref061","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1093\/infdis\/jit354","article-title":"Enhancement of adaptive immunity to Neisseria gonorrhoeae by local intravaginal administration of microencapsulated interleukin 12","volume":"208","author":"Y Liu","year":"2013","journal-title":"The Journal of infectious diseases"},{"issue":"1","key":"ppat.1008602.ref062","article-title":"Intravaginal administration of interleukin 12 during genital gonococcal infection in mice induces immunity to heterologous strains of","volume":"3","author":"Y Liu","year":"2018","journal-title":"Neisseria gonorrhoeae. mSphere"},{"key":"ppat.1008602.ref063","doi-asserted-by":"crossref","first-page":"151","DOI":"10.12688\/wellcomeopenres.14859.1","article-title":"Typing complex meningococcal vaccines to understand diversity and population structure of key vaccine antigens","volume":"3","author":"CMC 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Ohneck","year":"2012"},{"issue":"10","key":"ppat.1008602.ref067","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1128\/IAI.71.10.5576-5582.2003","article-title":"A gonococcal efflux pump system enhances bacterial survival in a female mouse model of genital tract infection","volume":"71","author":"AE Jerse","year":"2003","journal-title":"Infection and immunity"},{"issue":"8","key":"ppat.1008602.ref068","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1128\/JB.01833-06","article-title":"pilQ Missense mutations have diverse effects on PilQ multimer formation, piliation, and pilus function in Neisseria gonorrhoeae","volume":"189","author":"RA Helm","year":"2007","journal-title":"Journal of bacteriology"},{"issue":"3","key":"ppat.1008602.ref069","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1128\/JB.186.3.730-739.2004","article-title":"A mutant form of the Neisseria gonorrhoeae pilus secretin protein PilQ allows increased entry of heme and antimicrobial compounds","volume":"186","author":"CJ Chen","year":"2004","journal-title":"Journal of bacteriology"},{"issue":"11","key":"ppat.1008602.ref070","doi-asserted-by":"crossref","first-page":"6986","DOI":"10.1128\/AAC.03082-14","article-title":"In Vitro selection of Neisseria gonorrhoeae mutants with elevated MIC values and increased resistance to cephalosporins","volume":"58","author":"SR Johnson","year":"2014","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"9","key":"ppat.1008602.ref071","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/j.vaccine.2011.12.076","article-title":"Recombinant outer membrane secretin PilQ(406\u2013770) as a vaccine candidate for serogroup B Neisseria meningitidis","volume":"30","author":"F Haghi","year":"2012","journal-title":"Vaccine"},{"issue":"5","key":"ppat.1008602.ref072","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1365-2958.2005.04906.x","article-title":"Molecular architecture and function of the 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resistance gene as a gene cassette within a class 1 integron isolated from Escherichia coli","volume":"43","author":"D Sandvang","year":"1999","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"ppat.1008602.ref076","first-page":"Unit4A 2","article-title":"Genetic Manipulation of Neisseria gonorrhoeae","volume":"Chapter 4","author":"JP Dillard","year":"2011","journal-title":"Current protocols in microbiology"},{"issue":"Suppl 2","key":"ppat.1008602.ref077","doi-asserted-by":"crossref","first-page":"S375","DOI":"10.1086\/513847","article-title":"Human experimentation with Neisseria gonorrhoeae: progress and goals","volume":"179","author":"MS Cohen","year":"1999","journal-title":"The Journal of infectious diseases"},{"issue":"11","key":"ppat.1008602.ref078","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.1128\/IAI.67.11.5699-5708.1999","article-title":"Experimental gonococcal genital tract infection and opacity protein expression in estradiol-treated 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I. 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