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基于自我复制 RNA 脂质纳米颗粒的口服疫苗可同时中和 SARS-CoV-2 的阿尔法和德尔塔变体。

The oral vaccine based on self-replicating RNA lipid nanoparticles can simultaneously neutralize both SARS-CoV-2 variants alpha and delta.

机构信息

Sirjan School of Medical Sciences, Sirjan, Iran.

Medical Education Development Center, Sirjan School of Medical Sciences, Sirjan, Iran.

出版信息

Int Immunopharmacol. 2021 Dec;101(Pt B):108231. doi: 10.1016/j.intimp.2021.108231. Epub 2021 Oct 7.

Abstract

The aim of this study was to evaluate self-replicating RNA lipid nanoparticles (saRNA LNPs) to neutralize SARS-CoV-2 variants delta (B.1.617 lineage) and alpha (B.1.1.7 lineage). Before immunization of mice with saRNA LNPs, we saw high expression of S-protein at both mRNA and protein levels after transfection of HEK293T/17 cells with saRNA LNPs. After oral immunization of BALB/c mice with 0.1 - 10 µg saRNA LNPs , a high quantity of SARS-CoV-2 specific IgG and IgA antibodies were seen with a dose-dependent pattern. Importantly, the ratio of IgG2a/IgG1 in serum of vaccinated mice showed Th1/Th2 skewing response. We also found that the secreted antibodies could neutralize SARS-CoV-2 variants delta (B.1.617 lineage) and alpha (B.1.1.7 lineage). Re-stimulated splenocytes of vaccinated mice showed high secretion of IFN-γ, IL-6, and TNF- α . The authors think that although the preclinical study confirmed the efficacy of saRNA LNPs against SARS-CoV-2, the actual efficacy and safety of the oral vaccine must be evaluated in clinical trials.

摘要

本研究旨在评估自复制 RNA 脂质纳米颗粒(saRNA LNPs)对 SARS-CoV-2 变体 delta(B.1.617 谱系)和 alpha(B.1.1.7 谱系)的中和作用。在使用 saRNA LNPs 对小鼠进行免疫接种之前,我们观察到 saRNA LNPs 转染 HEK293T/17 细胞后,S 蛋白在 mRNA 和蛋白水平上均呈现高表达。经口免疫 BALB/c 小鼠 0.1-10μg saRNA LNPs 后,可观察到 SARS-CoV-2 特异性 IgG 和 IgA 抗体呈剂量依赖性增加。重要的是,疫苗接种小鼠血清中 IgG2a/IgG1 的比值显示出 Th1/Th2 偏向反应。我们还发现,分泌的抗体可以中和 SARS-CoV-2 变体 delta(B.1.617 谱系)和 alpha(B.1.1.7 谱系)。疫苗接种小鼠的再刺激脾细胞高分泌 IFN-γ、IL-6 和 TNF-α。作者认为,尽管临床前研究证实了 saRNA LNPs 对 SARS-CoV-2 的疗效,但口服疫苗的实际疗效和安全性必须在临床试验中进行评估。

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