{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:19:10Z","timestamp":1787026750722,"version":"build-2736575974"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"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. Microbiol."],"abstract":"<jats:p>\n                    Mice were immunized with a combination of self-amplifying (sa) RNA constructs for the F1 and V antigens of\n                    <jats:italic>Yersinia pestis<\/jats:italic>\n                    at a dose level of 1\u2009\u03bcg or 5\u2009\u03bcg or with the respective protein sub-units as a reference vaccine. The immunization of outbred OF1 mice on day 0 and day 28 with the lowest dose used (1\u2009\u03bcg) of each of the saRNA constructs in lipid nanoparticles protected 5\/7 mice against subsequent sub-cutaneous challenge on day 56 with 180\u2009cfu (2.8 MLD) of a 2021 clinical isolate of\n                    <jats:italic>Y. pestis<\/jats:italic>\n                    termed 10-21\/S whilst 5\/7 mice were protected against 1800cfu (28MLD) of the same bacteria on day 56. By comparison, only 1\/8 or 1\/7 negative control mice immunized with 10\u2009\u03bcg of irrelevant haemagglutin RNA in lipid nanoparticles (LNP) survived the challenge with 2.8 MLD or 28 MLD\n                    <jats:italic>Y. pestis<\/jats:italic>\n                    10-21\/S, respectively. BALB\/c mice were also immunized with the same saRNA constructs and responded with the secretion of specific IgG to F1 and V, neutralizing antibodies for the V antigen and developed a recall response to both F1 and V. These data represent the first report of an RNA vaccine approach using self-amplifying technology and encoding both of the essential virulence antigens, providing efficacy against\n                    <jats:italic>Y. pestis<\/jats:italic>\n                    . This saRNA vaccine for plague has the potential for further development, particularly since its amplifying nature can induce immunity with less boosting. It is also amenable to rapid manufacture with simpler downstream processing than protein sub-units, enabling rapid deployment and surge manufacture during disease outbreaks.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2023.1247041","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T01:53:55Z","timestamp":1698976435000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague"],"prefix":"10.3389","volume":"14","author":[{"given":"Robin John","family":"Shattock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Voahangy","family":"Andrianaivoarimanana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"McKay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovasoa Nomena","family":"Randriantseheno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valarmathy","family":"Murugaiah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Samnuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Rogers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Tregoning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoarisoa","family":"Rajerison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoffer M.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Robert","family":"Laws","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Diane","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"ref22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/immadv\/Itab020","article-title":"Potential human immunotherapeutics for plague","volume":"1","author":"Andrianaivoarimanana","year":"2021","journal-title":"Immunother. Adv."},{"key":"ref1","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1080\/21645515.2018.1527496","article-title":"The effect of antigen dose on T cell-targeting vaccine outcome","volume":"15","author":"Billeskov","year":"2019","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3390\/vaccines9020097","article-title":"An update on self-amplifying mRNA vaccine development","volume":"9","author":"Blakney","year":"","journal-title":"Vaccines"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1016\/j.ymthe.2020.11.011","article-title":"Innate inhibiting proteins enhance expression and immunogenicity of self-amplifying RNA","volume":"29","author":"Blakney","year":"","journal-title":"Mol. Ther."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/nrmicro1526","article-title":"The type III secretion injectisome","volume":"4","author":"Cornelis","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"ref5","first-page":"18","article-title":"La s\u00e9rologie anti-F1 chez la souris OF1, test compl\u00e9mentaire pour le diagnostic de la peste humaine","volume":"64","author":"Dromigny","year":"1998","journal-title":"Arch. Inst. Pasteur Madagascar"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"S178","DOI":"10.1093\/clinids\/21.supplement_2.s178","article-title":"Relationship between virulence and immunity as revealed in recent studies of the F1 capsule of Yersinia pestis","volume":"21","author":"Friedlander","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1128\/IAI.71.1.374-383.2003","article-title":"Effective protective immunity to Yersinia pestis infection conferred by DNA vaccine coding for derivatives of the F1 capsular antigen","volume":"71","author":"Grosfeld","year":"2003","journal-title":"Infect. Immun."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"731604","DOI":"10.1155\/2012\/731604","article-title":"Advanced development of the rF1V and rBV a\/B vaccines: progress and challenges","volume":"2012","author":"Hart","year":"2012","journal-title":"Adv. Prev. Med."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e10060","DOI":"10.1002\/amp2.10060","article-title":"Rapid development and deployment of high-volume vaccines for pandemic response","volume":"2","author":"Kis","year":"2020","journal-title":"J. Adv. Manuf. Process."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"eadg1036","DOI":"10.1126\/sciadv.adg1036","article-title":"A single-dose F1-based mRNA-LNP vaccine provides protection against the lethal plague bacterium","volume":"9","author":"Kon","year":"2023","journal-title":"Sci. Adv."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2854","DOI":"10.1128\/iai.63.8.2854-2858.1995","article-title":"Active immunization with recombinant V antigen from Yersinia pestis protects mice against plague","volume":"63","author":"Leary","year":"1995","journal-title":"Infect. Immun."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"6959","DOI":"10.1128\/JVI.00183-14","article-title":"Enhanced immunogenicity of an HIV-1 DNA vaccine delivered with electroporation via combined intramuscular and intradermal routes","volume":"88","author":"Mann","year":"2014","journal-title":"J. Virol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"3523","DOI":"10.1038\/s41467-020-17409-9","article-title":"Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice","volume":"11","author":"McKay","year":"2020","journal-title":"Nat. Commun."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/s41592-018-0224-7","article-title":"Comparing phenotypic variation between inbred and outbred mice","volume":"15","author":"Mogil","year":"2018","journal-title":"Nat. Methods"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3390\/vaccines10020145","article-title":"Predictors of survival after vaccination in a pneumonic plague model","volume":"10","author":"Moore","year":"2022","journal-title":"Vaccine"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1126\/science.1118476","article-title":"The V-antigen of Yersinia forms a distinct structure at the tip of injectisome needles","volume":"310","author":"Mueller","year":"2005","journal-title":"Science"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/S0035-9203(96)9042-4","article-title":"Comparison of Yersinia CIN agar and mouse inoculation assay for the diagnosis of plague","volume":"90","author":"Rasoamanana","year":"1996","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41541-019-0105-9","article-title":"Plague vaccine: recent progress and prospects","volume":"4","author":"Sun","year":"2019","journal-title":"NPJ Vaccines"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"101823","DOI":"10.1016\/j.eclinm.2022.101823","article-title":"COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2","volume":"56","author":"Szubert","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.1110\/ps.11101","article-title":"Macromolecular organization of the Yersinia pestis capsular F1 antigen: insights from time-of-flight mass spectrometry","volume":"10","author":"Tito","year":"2001","journal-title":"Protein Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.omtn.2022.11.024","article-title":"Formulation, inflammation, and RNA sensing impact the immunogenicity of self-amplifying RNA vaccines","volume":"31","author":"Tregoning","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref23","volume-title":"Plague vaccines workshop","year":"2018"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3598","DOI":"10.1128\/IAI.73.6.3598-3608.2005","article-title":"Human immune response to a plague vaccine comprising recombinant F1 and rV antigens","volume":"73","author":"Williamson","year":"2005","journal-title":"Infect. Immun."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1247041\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T01:53:59Z","timestamp":1698976439000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1247041\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,2]]},"references-count":24,"alternative-id":["10.3389\/fmicb.2023.1247041"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1247041","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,2]]},"article-number":"1247041"}}