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We assessed the toxicity and biodistribution of MRT5500, an mRNA vaccine encoding for the full\u2010length of the SARS\u2010CoV\u20102 spike protein and delivered by lipid nanoparticles (LNPs) containing a novel ionizable lipid, Lipid\u20101 in preclinical animal models. In the repeated dose toxicity study, rabbits received three intramuscular (IM) injections of MRT5500 at 3\u2010week interval followed by a 4\u2010week observation period. In an exploratory biodistribution study in mice receiving a single IM injection of an mRNA encoding luciferase encapsulated in an LNP containing Lipid\u20101, the expression of the luciferase protein was monitored in vivo and ex vivo at several time points. In the regulatory biodistribution study in rabbits receiving a single IM injection of MRT5500, the quantification of the mRNA and the ionizable Lipid\u20101 were monitored in the same organs and time points as in the exploratory biodistribution study. MRT5500 was safe and well\u2010tolerated with a transient acute phase response\/inflammation and an expected vaccine\u2010related immunological response, typical of those observed following a vaccine administration. The biodistribution data demonstrated that the mRNA and Lipid\u20101 components of the vaccine formulations were mainly detected at the injection site and in the draining lymph nodes. These results support the use of MRT5500 and its deployment into clinical trials.<\/jats:p>","DOI":"10.1002\/jat.4548","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:05:47Z","timestamp":1695081947000},"page":"371-390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Nonclinical safety assessment of an mRNA Covid\u201019 vaccine candidate following repeated administrations and biodistribution"],"prefix":"10.1002","volume":"44","author":[{"given":"Karine","family":"Broudic","sequence":"first","affiliation":[{"name":"Research and Development Sanofi  Marcy l'Etoile France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Laurent","sequence":"additional","affiliation":[{"name":"Research and Development Sanofi  Montpellier Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2429-056X","authenticated-orcid":false,"given":"Vladimir","family":"Perkov","sequence":"additional","affiliation":[{"name":"Research and Development Sanofi  Marcy l'Etoile France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlene","family":"Simon","sequence":"additional","affiliation":[{"name":"Research and Development Sanofi  Marcy l'Etoile France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Garinot","sequence":"additional","affiliation":[{"name":"Research and Development Sanofi  Marcy l'Etoile France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Truchot","sequence":"additional","affiliation":[{"name":"France Safety Assessment SAS Charles River Laboratories  Saint\u2010Germain\u2010Nuelles France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Latour","sequence":"additional","affiliation":[{"name":"Research and Development Sanofi  Marcy l'Etoile France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6012-8928","authenticated-orcid":false,"given":"Paul","family":"D\u00e9sert","sequence":"additional","affiliation":[{"name":"Research and Development Sanofi  Marcy l'Etoile France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2028436"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2010.00252.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035389"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3314"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2022.105189"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623320959090"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-7020-3519-7.00007-3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2022.116143"},{"key":"e_1_2_8_10_1","volume-title":"Study of mRNA vaccine formulation against COVID\u201019 in healthy adults 18 years of age and older","author":"ClinicalTrials.gov\u2010identifier: NCT04798027"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2013.04.003"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2009.01.007"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)08751-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581815598750"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.01.013"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00418-x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022483"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.09.026"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2022.01.021"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-021-00324-5"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.5b02497"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/amp2.10060"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-017-0032-6"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2017.0671"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2021.105029"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.243"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577"},{"issue":"2","key":"e_1_2_8_28_1","first-page":"174","article-title":"SARS\u2010CoV\u20102, SARS\u2010CoV, and MERS\u2010COV: A comparative overview","volume":"28","author":"Rabaan A. 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