Visualization of early events in mRNA vaccine delivery in non-human primates via PET–CT and near-infrared imaging
Abstract
Visualization of the spatio-temporal trafficking of vaccines after their delivery would help evaluate the efficacy of candidate formulations and aid their rational design for preclinical and translational studies. Here, we show that a dual radionuclide-near-infrared probe allows for quantitative, longitudinal and non-invasive monitoring, via positron emission tomography-computed tomography and near-infrared imaging of cynomolgus macaques, of the trafficking dynamics to draining lymph nodes of a model messenger RNA vaccine labelled with the probe. After intramuscular administration of the vaccine to the monkeys, we observed the dynamics of the mRNA vaccine at the injection site and in the draining lymph nodes, performed cellular analyses of the involved tissues using flow cytometry and identified through immunofluorescence that professional antigen-presenting cells are the primary cells containing the injected mRNA and encoding the antigen. This approach may reveal spatio-temporal determinants of vaccine efficacy in preclinical and translational studies employing large mammals.
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A yellow fever mRNA vaccine delivered by LNP was mainly expressed at the injection site as well as in draining lymph nodes in cynomolgus macaques.
“A recent study has shown that a yellow fever mRNA vaccine delivered by LNP was mainly expressed at the injection site as well as in draining lymph nodes in cynomolgus macaques (Lindsay et al., 2019).”
From A thermostable mRNA vaccine against COVID-19 (2020) · cites this paper as Lindsay et al., 2019
Encapsulating mRNA in LNPs enhances delivery to the cytosol of antigen-presenting cells.
“and enhances delivery to the cytosol of antigen-presenting cells (Liang et al., 2017, Lindsay et al., 2019).”
From mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability (2021) · cites this paper as Lindsay et al., 2019
Owing to their relatively small size, neutral surface charge and diffusible PEG lipid coating, mRNA LNPs might also enter the lymphatics to directly target lymph-node-resident antigen-presenting cells and B cells.
“owing to their relatively small size (~100 nm), neutral surface charge and diffusible PEG lipid coating, mRNA LNPs might also enter the lymphatics to directly target LN-resident APCs and B cells [11,58]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [58]
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- Authors
- Lindsay, K. E., Bhosle, S. M., Zurla, C., Beyersdorf, J., Rogers, K. A., Vanover, D., Xiao, P., Araínga, M., Shirreff, L. M., Pitard, B., Baumhof, P., Villinger, F., & Santangelo, P. J.
- Affiliations
- Georgia Institute of Technology (US)
- University of Louisiana at Lafayette (US)
- Inserm (FR)
- CureVac (Germany) (DE)
- Corresponding author
- Santangelo, Philip J.
- ORCID
- Venue
- Nature Biomedical Engineering
- Published
- 2019-04-01
- Volume
- 3
- Issue
- 5
- Pages
- 371-380
- ISSN
- 2157-846X (ISSN-L)
- OpenAlex
- W2927833149
- Cited by
- 218
- References
- 40
- Citations by year
- 2026: 23 · 2025: 42 · 2024: 38 · 2023: 34 · 2022: 31 · 2021: 36 · 2020: 10 · 2019: 4
- FWCI
- 13.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Georgia Institute of Technology
- Parker H. Petit Institute for Bioengineering and Bioscience
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- mRNA vaccine delivery, draining lymph nodes, PET/CT imaging, near-infrared imaging, cynomolgus macaques, antigen-presenting cells, intramuscular injection
- MeSH terms
- Positron Emission Tomography Computed Tomography, Animals, Antigen-Presenting Cells, Copper Radioisotopes, HeLa Cells, Humans, Lymph Nodes, Macaca fascicularis, Male, Muscles, RNA, Messenger, Vaccines, Gene Transfer Techniques, Spectroscopy, Near-Infrared
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