{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:29:02Z","timestamp":1790710142359,"version":"4.1.0"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Young Scientists Program of Guangzhou Laboratory","award":["QNPG24-06"],"award-info":[{"award-number":["QNPG24-06"]}]},{"name":"start-up and R&D Program of Guangzhou National Laboratory","award":["YW-JCZD0105"],"award-info":[{"award-number":["YW-JCZD0105"]}]},{"name":"Major Talent Project of Guangzhou National Laboratory","award":["GZNL2025C01020"],"award-info":[{"award-number":["GZNL2025C01020"]}]},{"name":"Guangzhou Science and Technology Program","award":["2023QN10Y428"],"award-info":[{"award-number":["2023QN10Y428"]}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2025A1515011053"],"award-info":[{"award-number":["2025A1515011053"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2024A1515010316"],"award-info":[{"award-number":["2024A1515010316"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the grant of State Key Laboratory of Respiratory Disease","award":["SKLRD-Z-202512"],"award-info":[{"award-number":["SKLRD-Z-202512"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Neisseria meningitidis<\/jats:italic>\n                    serogroup B (MenB) remains a major global cause of meningitis and septicemia. However, MenB vaccine development is hindered by antigenic diversity and manufacturing challenges associated with outer membrane vesicles (OMVs) or lipoproteins in resource-limited settings. Here, we engineered a high-purity circular RNA (circRNA) vaccine encoding a bacterial-derived, sequence-optimized fusion antigen of factor H binding protein (fHbp) and Neisserial heparin-binding antigen (NHBA) (fHbp-NHBA), which preserves key bactericidal epitopes in eukaryotic systems. The vaccine elicited potent functional antibody responses by serum bactericidal assay (SBA) using human complement and potent IFN-\u03b3-secreting CD8\u2009+\u2009T-cell responses. Crucially, the circRNA vaccine at a low dose provided complete protection and reduced bacteremia against lethal MenB challenge and demonstrated cross protection against a panel of prevalent strains in China. Both single- and two-dose regimens of the circRNA vaccine induced durable immune responses, and the two-dose immunization achieved strain coverage comparable to that of licensed MenB vaccines. Moreover, sera adoptively transferred from the circRNA-immunized group to neonatal rat pups dramatically reduced bacterial loads in blood. This study establishes a foundation for circRNA-based vaccines against bacterial pathogens.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013741","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:38:37Z","timestamp":1778521117000},"page":"e1013741","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["A circular RNA vaccine induces durable and cross-protective immunity against Neisseria meningitidis serogroup B in mice"],"prefix":"10.1371","volume":"22","author":[{"given":"Qiqi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyu","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusheng","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changbin","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixiong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhining","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyou","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuwen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6338-1418","authenticated-orcid":true,"given":"Shuai","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"issue":"4","key":"ppat.1013741.ref001","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jinf.2020.05.079","article-title":"The everchanging epidemiology of meningococcal disease worldwide and the potential for prevention through vaccination","volume":"81","author":"SR Parikh","year":"2020","journal-title":"J Infect"},{"issue":"6","key":"ppat.1013741.ref002","doi-asserted-by":"crossref","first-page":"106335","DOI":"10.1016\/j.jinf.2024.106335","article-title":"Global Meningococcal Initiative: Insights on antibiotic resistance, control strategies and advocacy efforts in Western Europe","volume":"89","author":"R Borrow","year":"2024","journal-title":"J Infect"},{"key":"ppat.1013741.ref003","doi-asserted-by":"crossref","first-page":"103571","DOI":"10.1016\/j.micpath.2019.103571","article-title":"Global estimate of Neisseria meningitidis serogroups proportion in invasive meningococcal disease: A systematic review and meta-analysis","volume":"134","author":"A Purmohamad","year":"2019","journal-title":"Microb Pathog"},{"issue":"16","key":"ppat.1013741.ref004","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1056\/NEJMra0906357","article-title":"Advances in the development of vaccines against Neisseria meningitidis","volume":"362","author":"LKK Tan","year":"2010","journal-title":"N Engl J Med"},{"issue":"6","key":"ppat.1013741.ref005","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1586\/erv.09.30","article-title":"Challenges and progress in the development of a serogroup B meningococcal vaccine","volume":"8","author":"S Lewis","year":"2009","journal-title":"Expert Rev Vaccines"},{"issue":"29","key":"ppat.1013741.ref006","doi-asserted-by":"crossref","first-page":"10834","DOI":"10.1073\/pnas.0603940103","article-title":"A universal vaccine for serogroup B meningococcus","volume":"103","author":"MM Giuliani","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"ppat.1013741.ref007","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1073\/pnas.0915162107","article-title":"Neisseria meningitidis GNA2132, a heparin-binding protein that induces protective immunity in humans","volume":"107","author":"D Serruto","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"16","key":"ppat.1013741.ref008","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1002\/1873-3468.13793","article-title":"Meningococcal factor H binding protein as immune evasion factor and vaccine antigen","volume":"594","author":"S Principato","year":"2020","journal-title":"FEBS Lett"},{"issue":"5","key":"ppat.1013741.ref009","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/S1473-3099(13)70341-4","article-title":"A vaccine against serogroup B Neisseria meningitidis: dealing with uncertainty","volume":"14","author":"SM Andrews","year":"2014","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"ppat.1013741.ref010","doi-asserted-by":"crossref","first-page":"4994","DOI":"10.1038\/s41467-020-18791-0","article-title":"Immunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity","volume":"11","author":"E Bartolini","year":"2020","journal-title":"Nat Commun"},{"issue":"9","key":"ppat.1013741.ref011","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(24)00031-8","article-title":"Use of a meningococcal group B vaccine (4CMenB) in populations at high risk of gonorrhoea in the UK","volume":"24","author":"SN Ladhani","year":"2024","journal-title":"Lancet Infect Dis"},{"issue":"5","key":"ppat.1013741.ref012","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s40259-015-0139-0","article-title":"Bivalent rLP2086 vaccine (Trumenba): a review in active immunization against invasive meningococcal group B disease in individuals aged 10-25 years","volume":"29","author":"M Shirley","year":"2015","journal-title":"BioDrugs"},{"issue":"49","key":"ppat.1013741.ref013","doi-asserted-by":"crossref","first-page":"7716","DOI":"10.1016\/j.vaccine.2020.08.031","article-title":"Broad vaccine protection against Neisseria meningitidis using factor H binding protein","volume":"38","author":"J Findlow","year":"2020","journal-title":"Vaccine"},{"issue":"1","key":"ppat.1013741.ref014","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/s41467-018-03146-7","article-title":"Structure-based design of chimeric antigens for multivalent protein vaccines","volume":"9","author":"S Hollingshead","year":"2018","journal-title":"Nat Commun"},{"issue":"10061","key":"ppat.1013741.ref015","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1016\/S0140-6736(16)31921-3","article-title":"Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational 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Memczak","year":"2013","journal-title":"Nature"},{"issue":"7441","key":"ppat.1013741.ref022","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature11993","article-title":"Natural RNA circles function as efficient microRNA sponges","volume":"495","author":"TB Hansen","year":"2013","journal-title":"Nature"},{"issue":"3","key":"ppat.1013741.ref023","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1093\/nar\/gkv1367","article-title":"Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor","volume":"44","author":"Y Enuka","year":"2016","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"ppat.1013741.ref024","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41392-021-00569-5","article-title":"Targeting circular RNAs as a therapeutic approach: current strategies and challenges","volume":"6","author":"AT He","year":"2021","journal-title":"Signal Transduct Target 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N6-methyladenosine","volume":"27","author":"Y Yang","year":"2017","journal-title":"Cell Res"},{"issue":"1","key":"ppat.1013741.ref029","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1038\/s41467-018-05096-6","article-title":"Engineering circular RNA for potent and stable translation in eukaryotic cells","volume":"9","author":"RA Wesselhoeft","year":"2018","journal-title":"Nat Commun"},{"issue":"3","key":"ppat.1013741.ref030","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.molcel.2019.02.015","article-title":"RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo","volume":"74","author":"RA Wesselhoeft","year":"2019","journal-title":"Molecular cell"},{"key":"ppat.1013741.ref031","doi-asserted-by":"crossref","first-page":"1258136","DOI":"10.3389\/fimmu.2023.1258136","article-title":"Glycosylation of bacterial antigens changes epitope patterns","volume":"14","author":"K Kern","year":"2023","journal-title":"Front 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Camperi","year":"2024","journal-title":"Analyt Chem"},{"issue":"7978","key":"ppat.1013741.ref035","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41586-023-06127-z","article-title":"Algorithm for optimized mRNA design improves stability and immunogenicity","volume":"621","author":"H Zhang","year":"2023","journal-title":"Nature"},{"issue":"1","key":"ppat.1013741.ref036","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/s41467-018-02827-7","article-title":"Crystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp","volume":"9","author":"J L\u00f3pez-Sagaseta","year":"2018","journal-title":"Nat Commun"},{"key":"ppat.1013741.ref037","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1107\/S2053230X17006021","article-title":"Crystal structures of human Fabs targeting the Bexsero meningococcal vaccine antigen NHBA","volume":"73","author":"M Maritan","year":"2017","journal-title":"Acta Crystallogr F Struct Biol Commun"},{"issue":"10","key":"ppat.1013741.ref038","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1008882","article-title":"4CMenB vaccine induces elite cross-protective human antibodies that compete with human factor H for binding to meningococcal fHbp","volume":"16","author":"D Veggi","year":"2020","journal-title":"PLoS Pathog"},{"issue":"11","key":"ppat.1013741.ref039","doi-asserted-by":"crossref","first-page":"12099","DOI":"10.1096\/fj.201900374R","article-title":"Cocrystal structure of meningococcal factor H binding protein variant 3 reveals a new crossprotective epitope recognized by human mAb 1E6","volume":"33","author":"F Bianchi","year":"2019","journal-title":"FASEB J"},{"issue":"9","key":"ppat.1013741.ref040","doi-asserted-by":"crossref","first-page":"3304","DOI":"10.1073\/pnas.1222845110","article-title":"Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine 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protein that elicits bactericidal antibody across antigenic variant groups","volume":"46","author":"PT Beernink","year":"2009","journal-title":"Mol Immunol"},{"issue":"24","key":"ppat.1013741.ref044","doi-asserted-by":"crossref","first-page":"4699","DOI":"10.1042\/BCJ20160806","article-title":"Neisseria meningitidis factor H-binding protein bound to monoclonal antibody JAR5: implications for antibody synergy","volume":"473","author":"E Malito","year":"2016","journal-title":"Biochem J"},{"issue":"2","key":"ppat.1013741.ref045","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1128\/IAI.00891-10","article-title":"Characterization of diverse subvariants of the meningococcal factor H (fH) binding protein for their ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies","volume":"79","author":"KL Seib","year":"2011","journal-title":"Infect 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