Impact of administration routes and dose frequency on the toxicology of SARS-CoV-2 mRNA vaccines in mice model
Rattachement africain : kr, pr. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
The increasing use of SARS-CoV-2 mRNA vaccines has raised concerns about their potential toxicological effects, necessitating further investigation to ensure their safety. To address this issue, we aimed to evaluate the toxicological effects of SARS-CoV-2 mRNA vaccine candidates formulated with four different types of lipid nanoparticles in ICR mice, focusing on repeated doses and administration routes. We conducted an extensive analysis in which mice received the mRNA vaccine candidates intramuscularly (50 μg/head) twice at 2-week intervals, followed by necropsy at 2 and 14 dpsi (days post-secondary injection). In addition, we performed a repeated dose toxicity test involving three, four, or five doses and compared the toxicological outcomes between intravenous and intramuscular routes. Our findings revealed that all vaccine candidates significantly induced SARS-CoV-2 spike protein-specific IgG and T cell responses. However, at 2 dpsi, there was a notable temporary decrease in lymphocyte and reticulocyte counts, anemia-related parameters, and significant increases in cardiac damage markers, troponin-I and NT-proBNP. Histopathological analysis revealed severe inflammation and necrosis at the injection site, decreased erythroid cells in bone marrow, cortical atrophy of the thymus, and increased spleen cellularity. While most toxicological changes observed at 2 dpsi had resolved by 14 dpsi, spleen enlargement and injection site damage persisted. Furthermore, repeated doses led to the accumulation of toxicity, and different administration routes resulted in distinct toxicological phenotypes. These findings highlight the potential toxicological risks associated with mRNA vaccines, emphasizing the necessity to carefully consider administration routes and dosage regimens in vaccine safety evaluations, particularly given the presence of bone marrow and immune organ toxicity, which, though eventually reversible, remains a serious concern.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Impact of administration routes and dose frequency on the toxicology of SARS-CoV-2 mRNA vaccines in mice model
- Date Crossref
- 10/12/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Seoul National University Hospital Department of Experiment Animal Research pays non établi dans la noticeÉtablissement de santé
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Catholic University of Korea Department of Medical and Biological Sciences pays non établi dans la noticeUniversité ou école supérieure
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The Catholic University of Korea Bucheon St. Mary's Hospital pays non établi dans la noticeÉtablissement de santé
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Seoul National University pays non établi dans la noticeUniversité ou école supérieure
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CHA University Department of Pathology pays non établi dans la noticeUniversité ou école supérieure
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CHA University Ilsan Medical Center pays non établi dans la noticeÉtablissement de santé
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Department of Experiment Animal Research — Seoul National University Hospital, Department of Medical and Biological Sciences — Catholic University of Korea et The Catholic University of Korea Bucheon St. Mary's Hospital, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.