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使用正电子发射断层扫描/计算机断层扫描（PET/CT）在体内监测mRNA疫苗抗原表达。

Monitoring mRNA vaccine antigen expression in vivo using PET/CT.

作者信息

Blizard Gabrielle S, Dwivedi Garima, Pan Yi-Gen, Hou Catherine, Etersque Jean M, Said Hooda, Chevrier Anik, Lavertu Marc, Ni Houping, Davis Benjamin, Tam Ying, Cao Quy, Mach Robert H, Weissman Drew, Alameh Mohamad-Gabriel, Sellmyer Mark A

机构信息

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

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Nat Commun. 2025 Mar 6;16(1):2234. doi: 10.1038/s41467-025-57446-w.

DOI:10.1038/s41467-025-57446-w
PMID:40044669
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11882883/
Abstract

Noninvasive visualization of the distribution and persistence of mRNA vaccine antigen expression in mammalian systems has implications for the development and evaluation of future mRNA vaccines. Here, we genetically fuse E. coli dihydrofolate reductase (eDHFR) to the delta furin diproline modified SARS-CoV-2 spike glycoprotein (S2P) mRNA vaccine and image its expression in female mice and male non-human primates using [F]fluoropropyl-trimethoprim ([F]FP-TMP). Whole body positron emission tomography (PET) imaging revealed transient expression of the vaccine antigen in the injection site and draining lymph nodes (dLNs). Fusion of eDHFR did not impact S2P immunogenicity and no humoral or cellular immune response was detected against eDHFR in either species. In this work, we show that eDHFR can be used as an mRNA-encoded PET reporter gene to monitor the spatiotemporal dynamics of mRNA vaccine antigen expression in vivo. This technique could be applied in clinical translation of future mRNA vaccines or therapeutics.

摘要

在哺乳动物系统中对mRNA疫苗抗原表达的分布和持续性进行无创可视化，对未来mRNA疫苗的开发和评估具有重要意义。在此，我们将大肠杆菌二氢叶酸还原酶（eDHFR）基因融合到经弗林蛋白酶切割位点双脯氨酸修饰的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突糖蛋白（S2P）mRNA疫苗上，并使用[F]氟丙基甲氧苄啶（[F]FP-TMP）对其在雌性小鼠和雄性非人类灵长类动物中的表达进行成像。全身正电子发射断层扫描（PET）成像显示疫苗抗原在注射部位和引流淋巴结（dLNs）中短暂表达。eDHFR的融合不影响S2P的免疫原性，并且在这两个物种中均未检测到针对eDHFR的体液或细胞免疫反应。在这项工作中，我们表明eDHFR可以用作mRNA编码的PET报告基因，以监测体内mRNA疫苗抗原表达的时空动态。该技术可应用于未来mRNA疫苗或治疗药物的临床转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/f6bfdc1633c6/41467_2025_57446_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/80fe22e86640/41467_2025_57446_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/54474cc6a80f/41467_2025_57446_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/913ecbf85280/41467_2025_57446_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/00e3b861b80f/41467_2025_57446_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/ffd7641d4068/41467_2025_57446_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/05b5f925be3a/41467_2025_57446_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/f6bfdc1633c6/41467_2025_57446_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/80fe22e86640/41467_2025_57446_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/54474cc6a80f/41467_2025_57446_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/913ecbf85280/41467_2025_57446_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/00e3b861b80f/41467_2025_57446_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/ffd7641d4068/41467_2025_57446_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/05b5f925be3a/41467_2025_57446_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300a/11882883/f6bfdc1633c6/41467_2025_57446_Fig7_HTML.jpg

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