{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:07:07Z","timestamp":1793416027682,"version":"4.5.0"},"reference-count":76,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP22fm0208101, JP23fm0208101, JP22ym0126815, JP23ym0126815, JP233fa627002"],"award-info":[{"award-number":["JP22fm0208101, JP23fm0208101, JP22ym0126815, JP23ym0126815, JP233fa627002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,6,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The mammarenavirus Lassa virus (LASV) causes the life-threatening hemorrhagic fever disease, Lassa fever. The lack of licensed medical countermeasures against LASV underscores the urgent need for the development of novel LASV vaccines, which has been hampered by the requirement for a biosafety level 4 facility to handle live LASV. Here, we investigated the efficacy of mRNA-lipid nanoparticle (mRNA-LNP)-based vaccines expressing the LASV glycoprotein precursor (LASgpc) or nucleoprotein (LCMnp) of the prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), in mice. Two doses of LASgpc- or LCMnp-mRNA-LNP administered intravenously (i.v.) protected C57BL\/6 mice from a lethal challenge with a recombinant (r) LCMV expressing a modified LASgpc (rLCMV\/LASgpc\n                      <jats:sup>2m<\/jats:sup>\n                      ) inoculated intracranially. Intramuscular (i.m.) immunization with two doses of LASgpc- or LCMnp-mRNA-LNP significantly reduced the viral load in C57BL\/6 mice inoculated i.v. with rLCMV\/LASgpc\n                      <jats:sup>2m<\/jats:sup>\n                      . High levels of viremia and lethality were observed in CBA mice inoculated i.v. with rLCMV\/LASgpc\n                      <jats:sup>2m<\/jats:sup>\n                      , which were abrogated by i.m. immunization with two doses of LASgpc-mRNA-LNP. The protective efficacy of two i.m. doses of LCMnp-mRNA-LNP was confirmed in a lethal hemorrhagic disease model of FVB mice i.v. inoculated with wild-type rLCMV. In all conditions tested, negligible and high levels of LASgpc- and LCMnp-specific antibodies were detected in mRNA-LNP-immunized mice, respectively, but robust LASgpc- and LCMnp-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell responses were induced. Accordingly, plasma from LASgpc-mRNA-LNP-immunized mice did not exhibit neutralizing activity. Our findings and surrogate mouse models of LASV infection, which can be studied at a reduced biocontainment level, provide a critical foundation for the rapid development of mRNA-LNP-based LASV vaccines.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Lassa virus (LASV) is a highly pathogenic mammarenavirus responsible for several hundred thousand infections annually in West African countries, causing a high number of lethal Lassa fever (LF) cases. Despite its significant impact on human health, clinically approved, safe, and effective medical countermeasures against LF are not available. The requirement of a biosafety level 4 facility to handle live LASV has been one of the main obstacles to the research and development of LASV countermeasures. Here, we report that two doses of mRNA-lipid nanoparticle-based vaccines expressing the LASV glycoprotein precursor (LASgpc) or nucleoprotein (LCMnp) of lymphocytic choriomeningitis virus (LCMV), a mammarenavirus genetically closely related to LASV, conferred protection to recombinant LCMV-based surrogate mouse models of lethal LASV infection. Notably, robust LASgpc- and LCMnp-specific CD8\n                        <jats:sup>+<\/jats:sup>\n                        T cell responses were detected in mRNA-LNP-immunized mice, whereas no virus-neutralizing activity was observed.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00578-24","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T09:01:06Z","timestamp":1716195666000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["An mRNA-LNP-based Lassa virus vaccine induces protective immunity in mice"],"prefix":"10.1128","volume":"98","author":[{"given":"Mei","family":"Hashizume","sequence":"first","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Takashima","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7117-461X","authenticated-orcid":true,"given":"Masaharu","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"},{"name":"Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka, Japan"},{"name":"Center for Advanced Modalities and Drug Delivery System, Osaka University, Suita, Osaka, Japan"},{"name":"RNA Frontier Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"1283","volume-title":"Fields virology","author":"Buchmeier MJ","year":"2013","unstructured":"Buchmeier MJ, de laJC, Peters CJ. 2013. Arenaviridae, p 1283\u20131303. In Kinpe DM, Howley PM (ed), Fields virology, 6th ed. Lippincott Williams & Wilkins.","edition":"6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000388"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7426.1271"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-71726-0_3"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.185.4147.263"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004957"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008811"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2017.304186"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10198-0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198601023140104"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0009522"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33112-3"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/2041-210X.12549"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01948-08"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2013.04.007"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix201"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1702(88)90033-0"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)90767-7"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI131958"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.78.10.5458-5465.2004"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020183"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90514-p"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.22.13934-13942.2005"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.12.001"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.11.079"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw3163"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abf6348"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37050-6"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2013.04.010"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2002.126297"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa053240"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/tid.12707"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073785"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp068021"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.12.2043"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00236-14"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01303-16"},{"key":"e_1_3_3_39_2","volume-title":"Science brief: COVID-19 vaccines and vaccination, CDC COVID-19 science briefsUnless a copyright is indicated, information on CDC\u2019s sites, blogs, and applications is in the public domain and may be copied and distributed without permission","author":"National Center for I, Respiratory Diseases DoVD","year":"2020","unstructured":"National Center for I, Respiratory Diseases DoVD. 2020. Science brief: COVID-19 vaccines and vaccination, CDC COVID-19 science briefs. Unless a copyright is indicated, information on CDC\u2019s sites, blogs, and applications is in the public domain and may be copied and distributed without permission. Centers for Disease Control and Prevention, Atlanta (GA)."},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03841-4"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm0829"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq347"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.06.008"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.1c00197"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.6b00090"},{"key":"e_1_3_3_46_2","first-page":"1831","article-title":"Lymphocytic choriomeningitis virus: pathogenesis of acute central nervous system disease","volume":"30","author":"Cole GA","year":"1971","unstructured":"Cole GA, Gilden DH, Monjan AA, Nathanson N. 1971. Lymphocytic choriomeningitis virus: pathogenesis of acute central nervous system disease. Fed Proc 30:1831\u20131841.","journal-title":"Fed Proc"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.1.317"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.74.15.6777-6783.2000"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11544"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.12.134"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12080896"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1408148111"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1804674115"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003073"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890370102"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01294-2"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.351.6268.16"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-10-52"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1200-9"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-67452-6_2"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00154-1"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00426-1"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4396"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(85)90388-8"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41376-6"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","unstructured":"Bukreyev A Kuzmin I Acosta RS Wasdin P Mire C Engdahl T Moon W Popov V Crowe J Georgiev I Garcia-Blanco M Abbott R. 2023. Andes virus mRNA vaccines: comparison of unmodified and modified mRNA platforms. In review. doi:10.21203\/rs.3.rs-3182841\/v1","DOI":"10.21203\/rs.3.rs-3182841\/v1"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00186-20"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00039-20"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03401-14"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02075-15"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1586\/erv.12.139"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-0669-6"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600652103"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.01.012"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900088106"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.12.6393-6397.2002"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(91)90018-u"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00578-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00578-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T09:33:43Z","timestamp":1718271223000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00578-24"}},"subtitle":[],"editor":[{"given":"Tom","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,6,13]]},"references-count":76,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6,13]]}},"alternative-id":["10.1128\/jvi.00578-24"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00578-24","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.04.03.535313","asserted-by":"object"}]},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,13]]},"assertion":[{"value":"2024-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00578-24"}}