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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
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    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.
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