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在体内使用PET/CT监测mRNA疫苗抗原表达

Gabrielle S Blizard^1,2, Garima Dwivedi^3,4, Yi-Gen Pan³

¹Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Nature communications

|March 5, 2025

概括

这项研究开发了一种新的方法,用于在体内可视化mRNA疫苗抗原表达. 在临床前模型中,该工程记者基因允许对疫苗分布和持续性的非侵入性跟踪.

科学领域:

生物技术是生物技术.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

对mRNA疫苗抗原表达的非侵入性成像对于疫苗开发和评估至关重要.
目前的方法缺乏在体内追踪抗原表达的时空动态的能力.

研究的目的:

开发和验证一种mRNA编码的记者基因系统,用于对疫苗抗原表达的非侵入性成像.
评估使用大肠杆菌二水叶酸还原酶 (eDHFR) 作为PET记者基因与SARS-CoV-2尖端糖蛋白mRNA疫苗融合的可行性.

主要方法:

基因融合了eDHFR到一个改造的SARS-CoV-2尖端糖蛋白 (S2PΔf) mRNA疫苗.
在雌性小鼠和雄性非人类灵长类动物中,使用[18F]烯酸三甲 ([18F]FP-TMP) 和正子发射断层扫描 (PET) 进行了对抗原表达的成像.
评估了S2P抗原的免疫性和对eDHFR的免疫反应.

主要成果:

全身PET成像显示了疫苗抗原在注射部位和排水淋巴结 (dLN) 的短暂表达.
eDHFR的融合没有影响S2P免疫性.
在这两种物种中都没有检测到对eDHFR的幽默或细胞免疫反应.

结论:

eDHFR作为一种可行的mRNA编码的PET记者基因,用于监测体内mRNA疫苗抗原表达动态.
这种技术为mRNA疫苗和治疗药物的临床翻译提供了一个有前途的工具.
抗原表达的非侵入性可视化可以帮助开发和评估基于mRNA的新型干预措施.

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