{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T15:00:39Z","timestamp":1772895639243,"version":"3.50.1"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.es","clinicalkey.com.au","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.tox.2025.154107","type":"journal-article","created":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T22:46:23Z","timestamp":1741473983000},"page":"154107","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Nonclinical safety and biodistribution evaluation of HC009 mRNA vaccine against COVID-19 in rat"],"prefix":"10.1016","volume":"514","author":[{"given":"Juan","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xicheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanqian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengyang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huafeng","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongsheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"10101","key":"10.1016\/j.tox.2025.154107_bib1","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/S0140-6736(17)31665-3","article-title":"Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial","volume":"390","author":"Alberer","year":"2017","journal-title":"Lancet"},{"issue":"2","key":"10.1016\/j.tox.2025.154107_bib2","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics13020206","article-title":"Lipid Nanoparticles as Delivery Systems for RNA-Based Vaccines","volume":"13","author":"Aldosari","year":"2021","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.tox.2025.154107_bib3","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2022.116143","article-title":"Nonclinical safety evaluation of a novel ionizable lipid for mRNA delivery","volume":"451","author":"Broudic","year":"2022","journal-title":"Toxicol. Appl. Pharm."},{"issue":"3","key":"10.1016\/j.tox.2025.154107_bib4","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/jat.4548","article-title":"Nonclinical safety assessment of an mRNA Covid-19 vaccine candidate following repeated administrations and biodistribution","volume":"44","author":"Broudic","year":"2024","journal-title":"J. Appl. Toxicol."},{"issue":"5","key":"10.1016\/j.tox.2025.154107_bib5","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1007\/s00204-021-03221-x","article-title":"Non-clinical immunogenicity, biodistribution and toxicology evaluation of a chimpanzee adenovirus-based COVID-19 vaccine in rat and rhesus macaque","volume":"96","author":"Dai","year":"2022","journal-title":"Arch. Toxicol."},{"issue":"14","key":"10.1016\/j.tox.2025.154107_bib6","doi-asserted-by":"crossref","first-page":"7790","DOI":"10.1128\/JVI.01244-13","article-title":"Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group","volume":"87","author":"de Groot","year":"2013","journal-title":"J. Virol."},{"key":"10.1016\/j.tox.2025.154107_bib7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.omtn.2019.01.013","article-title":"Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines","volume":"15","author":"Hassett","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.tox.2025.154107_bib8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41541-019-0132-6","article-title":"The how's and what's of vaccine reactogenicity","volume":"4","author":"Herve","year":"2019","journal-title":"NPJ Vaccin."},{"issue":"12","key":"10.1016\/j.tox.2025.154107_bib9","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid nanoparticles for mRNA delivery","volume":"6","author":"Hou","year":"2021","journal-title":"Nat. Rev. Mater."},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"9","key":"10.1016\/j.tox.2025.154107_bib11","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/j.vaccine.2022.01.021","article-title":"Pan-SARS neutralizing responses after third boost vaccination in non-human primate immunogenicity model","volume":"40","author":"Kalnin","year":"2022","journal-title":"Vaccine"},{"issue":"2","key":"10.1016\/j.tox.2025.154107_bib12","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1111\/jvim.17008","article-title":"Serum concentrations of complement C3 and C4 in dogs with idiopathic epilepsy","volume":"38","author":"Kang","year":"2024","journal-title":"J. Vet. Intern Med"},{"issue":"11","key":"10.1016\/j.tox.2025.154107_bib13","doi-asserted-by":"crossref","first-page":"7300","DOI":"10.1021\/acs.nanolett.5b02497","article-title":"Optimization of lipid nanoparticle formulations for mRNA delivery in vivo with fractional factorial and definitive screening designs","volume":"15","author":"Kauffman","year":"2015","journal-title":"Nano Lett."},{"key":"10.1016\/j.tox.2025.154107_bib14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2147\/JBM.S7224","article-title":"Homeostatic and pathogenic extramedullary hematopoiesis","volume":"1","author":"Kim","year":"2010","journal-title":"J. Blood Med"},{"issue":"2","key":"10.1016\/j.tox.2025.154107_bib15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.5625\/lar.2012.28.2.115","article-title":"Historical control data from 13-week repeated toxicity studies in Crj:CD (SD) rats","volume":"28","author":"Lee","year":"2012","journal-title":"Lab Anim. Res"},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib16","doi-asserted-by":"crossref","DOI":"10.3390\/molecules25010177","article-title":"Evaluation procoagulant activity and mechanism of astragalin","volume":"25","author":"Li","year":"2020","journal-title":"Molecules"},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib17","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1080\/21505594.2021.1871823","article-title":"Host defence RNases as antiviral agents against enveloped single stranded RNA viruses","volume":"12","author":"Li","year":"2021","journal-title":"Virulence"},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib18","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41541-024-00925-w","article-title":"Safety and efficacy assessment of an mRNA rabies vaccine in dogs, rodents, and cynomolgus macaques","volume":"9","author":"Li","year":"2024","journal-title":"NPJ Vaccin."},{"key":"10.1016\/j.tox.2025.154107_bib19","doi-asserted-by":"crossref","first-page":"1416375","DOI":"10.3389\/fimmu.2024.1416375","article-title":"Immunogenicity and protective efficacy of the HC009 mRNA vaccine against SARS-CoV-2","volume":"15","author":"Liu","year":"2024","journal-title":"Front. Immunol."},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib20","first-page":"S232","article-title":"The role of inflammation in CNS injury and disease","volume":"147","author":"Lucas","year":"2006","journal-title":"Br. J. Pharmacol."},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41580-021-00432-z","article-title":"Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design","volume":"23","author":"Malone","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib22","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1080\/08923973.2018.1533967","article-title":"Hematological and immunological impairment following in-utero and postnatal exposure to aluminum sulfate in female offspring of albino rats","volume":"41","author":"Omran","year":"2019","journal-title":"Immunopharmacol. Immunotoxicol."},{"issue":"2","key":"10.1016\/j.tox.2025.154107_bib23","doi-asserted-by":"crossref","first-page":"71","DOI":"10.5694\/mja2.51620","article-title":"mRNA vaccines: a transformative technology with applications beyond COVID-19","volume":"217","author":"Overmars","year":"2022","journal-title":"Med. J. Aust."},{"issue":"5","key":"10.1016\/j.tox.2025.154107_bib24","doi-asserted-by":"crossref","DOI":"10.1038\/cti.2017.19","article-title":"Corrigendum: A generalized quantitative antibody homeostasis model: antigen saturation, natural antibodies and a quantitative antibody network","volume":"6","author":"Prechl","year":"2017","journal-title":"Clin. Transl. Immunol."},{"issue":"5","key":"10.1016\/j.tox.2025.154107_bib25","doi-asserted-by":"crossref","first-page":"319","DOI":"10.4155\/tde-2016-0006","article-title":"mRNA vaccine delivery using lipid nanoparticles","volume":"7","author":"Reichmuth","year":"2016","journal-title":"Ther. Deliv."},{"issue":"2","key":"10.1016\/j.tox.2025.154107_bib26","article-title":"Toxicological assessments of a pandemic COVID-19 vaccine-demonstrating the suitability of a platform approach for mRNA vaccines","volume":"11","author":"Rohde","year":"2023","journal-title":"Vaccin. (Basel)"},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib27","first-page":"41","article-title":"Laboratory animal veterinary medicine","volume":"243","author":"Ryden","year":"2013","journal-title":"J. Am. Vet. Med Assoc."},{"issue":"6","key":"10.1016\/j.tox.2025.154107_bib28","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004746","article-title":"An mRNA Vaccine Encoding Rabies Virus Glycoprotein Induces Protection against Lethal Infection in Mice and Correlates of Protection in Adult and Newborn Pigs","volume":"10","author":"Schnee","year":"2016","journal-title":"PLoS Negl. Trop. Dis."},{"issue":"2","key":"10.1016\/j.tox.2025.154107_bib29","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1177\/0192623319875085","article-title":"Scientific and Regulatory Policy Committee Points to Consider*\u2009: Approaches to the Conduct and Interpretation of Vaccine Safety Studies for Clinical and Anatomic Pathologists","volume":"48","author":"Sellers","year":"2020","journal-title":"Toxicol. Pathol."},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib30","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41392-021-00750-w","article-title":"The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice","volume":"6","author":"Sun","year":"2021","journal-title":"Signal Transduct. Target Ther."},{"issue":"5","key":"10.1016\/j.tox.2025.154107_bib31","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1080\/01926230600964706","article-title":"Histopathology of bone marrow","volume":"34","author":"Travlos","year":"2006","journal-title":"Toxicol. Pathol."},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib32","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/nan.12444","article-title":"Review: Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies","volume":"44","author":"van Vliet","year":"2018","journal-title":"Neuropathol. Appl. Neurobiol."},{"issue":"7853","key":"10.1016\/j.tox.2025.154107_bib33","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41586-021-03275-y","article-title":"BNT162b vaccines protect rhesus macaques from SARS-CoV-2","volume":"592","author":"Vogel","year":"2021","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.tox.2025.154107_bib34","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/0887-2333(94)90073-6","article-title":"Principles for the validation of in vitro toxicology test methods","volume":"8","author":"Walum","year":"1994","journal-title":"Toxicol. Vitr."},{"issue":"6","key":"10.1016\/j.tox.2025.154107_bib35","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1177\/0192623319867053","article-title":"Nonproliferative and Proliferative Lesions of the Rat and Mouse Hematolymphoid System","volume":"47","author":"Willard-Mack","year":"2019","journal-title":"Toxicol. Pathol."},{"issue":"3","key":"10.1016\/j.tox.2025.154107_bib36","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1254\/fpj.133.154","article-title":"[Evaluation methods for nephrotoxicity]","volume":"133","author":"Yamada","year":"2009","journal-title":"Nihon Yakurigaku Zasshi"},{"issue":"1","key":"10.1016\/j.tox.2025.154107_bib37","doi-asserted-by":"crossref","first-page":"2190690","DOI":"10.1080\/21645515.2023.2190690","article-title":"Interim analysis of a phase 1 randomized clinical trial on the safety and immunogenicity of the mRNA-1283 SARS-CoV-2 vaccine in adults","volume":"19","author":"Yassini","year":"2023","journal-title":"Hum. Vaccin. Immunother."},{"issue":"7798","key":"10.1016\/j.tox.2025.154107_bib38","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"issue":"8","key":"10.1016\/j.tox.2025.154107_bib39","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus from Patients with Pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X25000630?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X25000630?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T11:13:42Z","timestamp":1744370022000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X25000630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":39,"alternative-id":["S0300483X25000630"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2025.154107","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Nonclinical safety and biodistribution evaluation of HC009 mRNA vaccine against COVID-19 in rat","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2025.154107","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"154107"}}