IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-57446-w.html
   My bibliography  Save this article

Monitoring mRNA vaccine antigen expression in vivo using PET/CT

Author

Listed:
  • Gabrielle S. Blizard

    (University of Pennsylvania
    University of Pennsylvania)

  • Garima Dwivedi

    (University of Pennsylvania
    University of Pennsylvania)

  • Yi-Gen Pan

    (University of Pennsylvania)

  • Catherine Hou

    (University of Pennsylvania)

  • Jean M. Etersque

    (University of Pennsylvania
    University of Pennsylvania)

  • Hooda Said

    (Children’s Hospital of Philadelphia)

  • Anik Chevrier

    (Polytechnique Montreal)

  • Marc Lavertu

    (Polytechnique Montreal)

  • Houping Ni

    (University of Pennsylvania
    University of Pennsylvania)

  • Benjamin Davis

    (University of Pennsylvania
    University of Pennsylvania)

  • Ying Tam

    (Acuitas Therapeutics)

  • Quy Cao

    (University of Pennsylvania)

  • Robert H. Mach

    (University of Pennsylvania)

  • Drew Weissman

    (University of Pennsylvania
    University of Pennsylvania)

  • Mohamad-Gabriel Alameh

    (University of Pennsylvania
    University of Pennsylvania
    Children’s Hospital of Philadelphia
    University of Pennsylvania)

  • Mark A. Sellmyer

    (University of Pennsylvania
    University of Pennsylvania)

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∆f) mRNA vaccine and image its expression in female mice and male non-human primates using [18F]fluoropropyl-trimethoprim ([18F]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.

Suggested Citation

  • Gabrielle S. Blizard & Garima Dwivedi & Yi-Gen Pan & Catherine Hou & Jean M. Etersque & Hooda Said & Anik Chevrier & Marc Lavertu & Houping Ni & Benjamin Davis & Ying Tam & Quy Cao & Robert H. Mach & , 2025. "Monitoring mRNA vaccine antigen expression in vivo using PET/CT," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57446-w
    DOI: 10.1038/s41467-025-57446-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-57446-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-57446-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Kathrin Leppek & Gun Woo Byeon & Wipapat Kladwang & Hannah K. Wayment-Steele & Craig H. Kerr & Adele F. Xu & Do Soon Kim & Ved V. Topkar & Christian Choe & Daphna Rothschild & Gerald C. Tiu & Roger We, 2022. "Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    2. Jean M. Etersque & Iris K. Lee & Nitika Sharma & Kexiang Xu & Andrew Ruff & Justin D. Northrup & Swarbhanu Sarkar & Tommy Nguyen & Richard Lauman & George M. Burslem & Mark A. Sellmyer, 2023. "Regulation of eDHFR-tagged proteins with trimethoprim PROTACs," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Sebastian Castillo-Hair & Stephen Fedak & Ban Wang & Johannes Linder & Kyle Havens & Michael Certo & Georg Seelig, 2024. "Optimizing 5’UTRs for mRNA-delivered gene editing using deep learning," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Tin-Lok Wong & Jia-Jian Loh & Shixun Lu & Helen H. N. Yan & Hoi Cheong Siu & Ren Xi & Dessy Chan & Max J. F. Kam & Lei Zhou & Man Tong & John A. Copland & Leilei Chen & Jing-Ping Yun & Suet Yi Leung &, 2023. "ADAR1-mediated RNA editing of SCD1 drives drug resistance and self-renewal in gastric cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Wenjing Bai & Jinxin Xu & Wenbin Gu & Danyang Wang & Ying Cui & Weidong Rong & Xiaoan Du & Xiaoxia Li & Cuicui Xia & Qingqing Gan & Guantao He & Huahui Guo & Jinfeng Deng & Yuqiong Wu & Ray-Whay Chiu , 2025. "Defining ortholog-specific UHRF1 inhibition by STELLA for cancer therapy," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    4. Zhijin Tian & Dandan Shao & Linlin Tang & Zhen Li & Qian Chen & Yongxiu Song & Tao Li & Friedrich C. Simmel & Jie Song, 2024. "Circular single-stranded DNA as a programmable vector for gene regulation in cell-free protein expression systems," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57446-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.