Visualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates
mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following intramuscular injection, we observed LNPs distributing through injected muscle tissue, simultaneous with rapid trafficking to draining lymph nodes (dLNs). Deltoid injection of LNPs mimicking human vaccine administration led to stochastic LNP delivery to three different sets of dLNs. LNP uptake in dLNs was confirmed by histology, and cellular analysis of tissues via flow cytometry identified antigen-presenting cells as the primary immune cell type responsible for early LNP uptake and mRNA translation. These results provide insights into the biodistribution of mRNA vaccines administered at clinically relevant doses, injection volumes, and injection sites in an important large animal model for vaccine development.
Authors
- Jon M. Steichen (ORCID: https://orcid.org/0000-0002-4586-3251)
- Maureen Buckley (ORCID: https://orcid.org/0000-0002-9928-6402)
- Jonathan Dye (ORCID: https://orcid.org/0000-0003-2801-8053)
- Laura Maiorino (ORCID: https://orcid.org/0000-0001-8217-1337)
- François Villinger (ORCID: https://orcid.org/0000-0002-7790-2008)
- Ivan S. Pires (ORCID: https://orcid.org/0000-0002-4035-0027)
- William R. Schief (ORCID: https://orcid.org/0000-0002-1120-0150)
- Katarzyna Kaczmarek Michaels (ORCID: https://orcid.org/0000-0002-2525-5830)
- Kashif Qureshi (ORCID: https://orcid.org/0009-0002-7734-0567)
- Mariluz Araínga (ORCID: https://orcid.org/0000-0002-4533-5854)
- Yiming J. Zhang (ORCID: https://orcid.org/0000-0002-8102-3815)
- Darrell J. Irvine (ORCID: https://orcid.org/0000-0002-8637-1405)
- Howard Mak
- Beomjoon Kim (ORCID: https://orcid.org/0000-0001-9565-299X)
Institutions
- Scripps Research Institute (US)
- Howard Hughes Medical Institute (US)
- Massachusetts Institute of Technology (US)
- University of Louisiana at Lafayette (US)
Publication Details
- Journal
- Molecular Therapy
- Published
- 2025-01-09
- DOI
- https://doi.org/10.1016/j.ymthe.2025.01.008
- Citations
- 26
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 36.30
Funders
- Howard Hughes Medical Institute
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- National Institutes of Health
- National Cancer Institute