不同mRNA-LNP疫苗剂量对BALB/c小鼠神经炎症的影响

IF 0.2 Q4 MEDICINE, GENERAL & INTERNAL
AS Kirshina, AA Kazakova, E. Kolosova, EA Imasheva, O. Vasileva, OV Zaborova, IM Terenin, A. Muslimov, VV Reshetnikov
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引用次数: 2

摘要

事实证明,mRNA疫苗对COVID-19疫情非常有效,而且副作用发生率低。然而,我们对核酸作为脂质纳米颗粒(LNPs)组分的生物学和生物安全性的理解仍有许多空白,LNPs通常被用作mrna基疫苗的细胞内递送系统。已知LNPs可引起严重的注射部位炎症,具有广泛的生物分布,并且在给药后可在包括大脑在内的身体多个组织中发现。具有这种药代动力学的新药物在难以接近的器官中发生炎症的作用尚不清楚。本研究旨在评估不同剂量表达报告蛋白(编码萤火虫荧光素酶的mRNA分别为0、5、10和20 μg)的mRNA-LNP对实验动物肌肉注射LNP纳米乳后4、8和30 h前额叶皮层和下丘脑神经炎症标志物(Tnfα、il - 1β、Gfap、Aif1)表达的影响。结果表明,接种10-20 μg mRNA的mRNA- lnp疫苗后8 h可增强下丘脑中Aif1的表达,但接种30 h后无明显差异。不同时间各组下丘脑中Gfap、l11β、Tnfα的表达水平存在差异。结果表明,经肠外给药的mRNA-LNPs可在一定时间间隔内刺激小胶质细胞的暂时激活,且具有剂量依赖性和部位特异性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of various mRNA-LNP vaccine doses on neuroinflammation in BALB/c mice
It has been proven that mRNA vaccines are highly effective against the COVID-19 outbreak, and low prevalence of side effects has been shown. However, there are still many gaps in our understanding of the biology and biosafety of nucleic acids as components of lipid nanoparticles (LNPs) most often used as a system for inctracellular delivery of mRNA-based vaccines. It is known that LNPs cause severe injection site inflammation, have broad biodistribution profiles, and are found in multiple tissues of the body, including the brain, after administration. The role of new medications with such pharmacokinetics in inflammation developing in inaccessible organs is poorly understood. The study was aimed to assess the effects of various doses of mRNA-LNP expressing the reporter protein (0, 5, 10, and 20 μg of mRNA encoding the firefly luciferase) on the expression of neuroinflammation markers (Tnfα, Il1β, Gfap, Aif1) in the prefrontal cortex and hypothalamus of laboratory animals 4, 8, and 30 h after the intramuscular injection of LNP nanoemulsion. It was shown that mRNA-LNP vaccines in a dose of 10–20 μg of mRNA could enhance Aif1 expression in the hypothalamus 8 h after vaccination, however, no such differences were observed after 30 h. It was found that the Gfap, l11β, Tnfα expression levels in the hypothalamus observed at different times in the experimental groups were different. According to the results, mRNA-LNPs administered by the parenteral route can stimulate temporary activation of microglia in certain time intervals in the dose-dependent and site specific manner.
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来源期刊
Bulletin of Russian State Medical University
Bulletin of Russian State Medical University MEDICINE, GENERAL & INTERNAL-
CiteScore
0.80
自引率
0.00%
发文量
59
期刊介绍: Bulletin of Russian State Medical University (Bulletin of RSMU, ISSN Print 2500–1094, ISSN Online 2542–1204) is a peer-reviewed medical journal of Pirogov Russian National Research Medical University (Moscow, Russia). The original language of the journal is Russian (Vestnik Rossiyskogo Gosudarstvennogo Meditsinskogo Universiteta, Vestnik RGMU, ISSN Print 2070–7320, ISSN Online 2070–7339). Founded in 1994, it is issued once every two months publishing articles on clinical medicine and medical and biological sciences, first of all oncology, neurobiology, allergy and immunology, medical genetics, medical microbiology and infectious diseases. Every issue is thematic. Deadlines for manuscript submission are announced in advance. The number of publications on topics in spite of the issue topic is limited. The journal accepts only original articles submitted by their authors, including articles that present methods and techniques, clinical cases and opinions. Authors must guarantee that their work has not been previously published elsewhere in whole or in part and in other languages and is not under consideration by another scientific journal. The journal publishes only one review per issue; the review is ordered by the editors.
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