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在mRNA和腺病毒COVID-19疫苗接种后,骨髓细胞中的剂量依赖性干扰素程序
Giray Naim Eryilmaz1, Yilmaz Yucehan Yazici1, Radu Marches1
1The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
bioRxiv : the preprint server for biology
|September 2, 2025
概括
这项研究显示,在第一次mRNACOVID-19疫苗注射后,骨髓细胞中出现了独特的,短暂的干扰素反应,与后来的剂量或腺病毒疫苗不同. 这些发现有助于优化疫苗策略.
科学领域:
- 免疫学
- 疫苗学
- 分子生物学
背景情况:
- 由于COVID-19大流行,需要快速开发疫苗,利用mRNA和病毒载体等多种平台.
- 了解不同疫苗平台引起的免疫反应的细微差别对于优化疫苗疗效和计划至关重要.
研究的目的:
- 在单细胞多原子分辨率下直接比较三种FDA批准的COVID-19疫苗 (BNT162b2,mRNA-1273,Ad26.COV2.S) 的纵向免疫反应.
- 阐明初级疫苗接种后骨髓细胞中干扰素的独特编程与不同疫苗平台的增强.
主要方法:
- 用BNT162b2,mRNA-1273或Ad26.COV2.S接种的 SARS-CoV-2原始成年人 (n=31) 的纵向分析.
- 血细胞因子水平,抗体标位和单细胞多基因数据的整合 (DOGMA-seq).
- 用干扰素对人类单细胞进行体外刺激,以模拟观察到的细胞状态.
主要成果:
- 在第一剂mRNA疫苗注射后1至2天内,约10%的骨髓细胞中发现了独特的,短暂的干扰素刺激基因 (ISG) - dim程序.
- 以ISGF3激活为特征的ISG- dim状态在转录和表观遗传上不同于在mRNA增强或Ad26. COV2. S疫苗接种后观察到的ISG- 高状态.
- 在体外研究表明,IFN-α单独诱导ISG-dim,而IFN-α和IFN-γ对于ISG高都需要.
结论:
- 干扰素在骨髓细胞中的编程取决于剂量和特定平台.
- 在初始注射和随后的增剂之间存在机制上的差异.
- 这些发现对优化COVID-19疫苗平台选择,剂量间隔和配方策略有影响.
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