ArticleMolecular pharmaceutics2023
Delivery and Expression of mRNA in the Secondary Lymphoid Organs Drive Immune Responses to Lipid Nanoparticle-mRNA Vaccines after Intramuscular Injection.
Article in Molecular pharmaceutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Combined HER2-targeted mRNA-LNP vaccine and radiotherapy suppress Lewis lung carcinoma growth in mice: Efficacy and mechanistic insights.Bioengineering & translational medicine · 2026Article
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Using an RNA binding protein to detect mRNA on lipid nanoparticles.Scientific reports · 2026Article
- Programmable lipid nanoparticles for RNA therapeutics: Design principles and clinical translation.Materials today. Bio · 2026Review
- Myomerger-derived peptide enhances skeletal muscle tropism and reduces liver transduction of lipid nanoparticles for gene delivery.Molecular therapy. Nucleic acids · 2026Article
- Combining Anti-Inflammatory Drugs and Cell-Specific Expression-Suppression Reduces the Adjuvant Activity of mRNA-LNPs.Molecular pharmaceutics · 2026Article
- mRNA-based SARS-CoV-2 vaccines: intracellular processing and aggregation of the encoded spike protein as a mechanistic contributor to cardiac cellular stress.Frontiers in immunology · 2026Article
- The design, manufacture and LNP formulation of mRNA for research use.Nature protocols · 2025Article
- mRNA vaccine platforms and novel delivery systems: From mechanistic principles to clinical translation.Human vaccines & immunotherapeutics · 2025Review
- RNA-based cancer vaccines: mechanisms, clinical progress, and translational challenges.Immunologic research · 2025Review
- Ionizable guanidine-based lipid nanoparticle for targeted mRNA delivery and cancer immunotherapy.Science advances · 2025Article
- Emerging lipid nanoparticle systems capable of efficient intramuscular RNA delivery.Nanomedicine (London, England) · 2025Review
- Review
- Innovative design and comprehensive characterization of a valine-enhanced lipid nanoparticle-coated mRNA vaccine targeting the SARS-CoV-2 S-RBD antigen.Scientific reports · 2025Article
- Positron Emission Tomography-Based Pharmacokinetics of mRNA-Lipid Nanoparticles: A Study Quantifying the ApoE and Macrophage Contribution.ACS applied materials & interfaces · 2025Article
- mRNAdesigner: an integrated web server for optimizing mRNA design and protein translation in eukaryotes.Nucleic acids research · 2025Article
- Evaluation of oral and injectable liposome-based vaccines with synthesized lipid for Japanese encephalitis virus in Sprague-Dawley rats.Clinical and experimental vaccine research · 2025Article
- mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting.Molecular therapy. Methods & clinical development · 2024Article
- Review
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipid nanoparticles (LNPs) are the prime delivery vehicle for mRNA vaccines. Previous hypotheses suggested that LNPs contribute to innate reactogenicity and lead to the establishment of a vaccine adaptive response. It has not been clear whether LNP adjuvancy in the muscle is the prime driver of adaptive immune responses or whether delivery to secondary lymphatic organs is necessary to induce strong adaptive responses. To address this, we formulated reporter gene (NLuc) or OVA mRNA into LNP or coadministered the mRNA with empty LNP. After IM injection, we correlated the delivery with adaptive immune responses. Additionally, we investigated humoral responses to modified mRNA encoding the SARS-CoV-2 spike protein. Compared to unformulated mRNA encoding nanoluciferase, with or without co-administered empty LNPs, LNP-formulated mRNA resulted in high levels of nanoluciferase in the secondary lymphoid organs. Similarly, LNP-mRNA encoding ovalbumin led to a cellular immune response against OVA while free mRNA, with or without empty adjuvanted LNPs, caused little or no immune response. Finally, only mice injected with LNP-formulated mRNA encoding SARS-CoV-2 spike protein elicited robust cellular and humoral immune responses. Our results suggest that the mRNA delivery and transfection of secondary lymphatic organs, not LNP adjuvancy or RNA expression in muscle, are the main drivers for adaptive immune response in mice. This work informs the design of next-generation mRNA delivery systems where better delivery to secondary lymphatic organs should lead to a better vaccine response.
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