Differential clearance rate of proteins encoded on a self-amplifying mRNA COVID-19 vaccine in muscle and lymph nodes

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2025-04-02 DOI:10.1016/j.bbrep.2025.101999

Reo Kanechi , Tatsuya Shishido , Mana Tachikawa , Tomohiro Nishimura , Akihito Sawada , Hayato Okade , Daisuke Ishikawa , Hitoshi Yamaguchi , Marito Araki

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Abstract

ARCT-154, a recently approved self-amplifying mRNA (saRNA) vaccine for SARS-CoV-2, has shown superior induction and prolonged maintenance of neutralizing antibodies compared to the conventional mRNA vaccine BNT162b2. However, the scientific evidence explaining this superiority remained elusive. Hence, we explored the temporal changes in spike protein and replicase components following a single dose of ARCT-154 vaccination in mice. The encoded spike protein reached its highest level approximately 3 days after vaccination and quickly disappeared from the rectus femoris muscle, the injection site. Although the spike protein levels also peaked at an early time point in the lymph nodes, it remained detectable 28 days after the vaccination and then disappeared by 44 days after the vaccination. Expression of nsP1, nsP2 and nsP4 was observed in the injected muscle and/or the lymph nodes for up to 15 days post-vaccination. Data were analyzed using unpaired two-tailed Mann–Whitney U-tests. These data suggest that prolonged expression of spike proteins in lymph nodes may, if not entirely, be responsible for the induction of higher and prolonged levels of neutralizing antibodies by the saRNA vaccine.

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自扩增mRNA COVID-19疫苗编码蛋白在肌肉和淋巴结中的差异清除率

与传统的mRNA疫苗BNT162b2相比，最近批准的SARS-CoV-2自扩增mRNA （saRNA）疫苗ARCT-154显示出更优越的诱导和长期维持中和抗体的能力。然而，解释这种优势的科学证据仍然难以捉摸。因此，我们探索了单剂量ARCT-154疫苗接种小鼠后刺突蛋白和复制酶成分的时间变化。编码的刺突蛋白在接种后约3天达到最高水平，并迅速从注射部位股直肌中消失。虽然刺突蛋白水平也在淋巴结的早期时间点达到峰值，但在接种疫苗后28天仍可检测到，然后在接种疫苗后44天消失。nsP1、nsP2和nsP4的表达在注射后的肌肉和/或淋巴结中观察到长达15天。数据分析采用非配对双尾Mann-Whitney u检验。这些数据表明，如果不是全部的话，淋巴结中刺突蛋白的长时间表达可能是saRNA疫苗诱导更高和更长水平的中和抗体的原因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.