ArticleNature biomedical engineering2025
Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccines by adjuvanting the ionizable lipid and the mRNA.
Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 79 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
79 citing papers in PubMed, 133 citations in OpenAlex.
- Novel lipid nanoparticle in a mRNA cancer vaccine drives tumor control via type I IFNs and effector CD8Molecular therapy. Nucleic acids · 2026Article
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- Engineering tolerogenic mRNA-LNPs for allergen-specific immune reprogramming in pollen allergy.Materials today. Bio · 2026Article
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Combinatorial synthesis of novel polycations for mRNA deliveryRSC applied polymers · 2026Article
- mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.Molecular biomedicine · 2026Review
- Low reactogenicity and high tumour antigen expression from mRNA-LNPs with membrane-destabilizing zwitterionic lipids.Nature biomedical engineering · 2026Article
- A novel machine learning framework-based rapid screening of ionizable lipids in LNPs for highly-efficient mRNA expression.Acta pharmaceutica Sinica. B · 2026Article
- Review
- Rational Design of Amphiphilic Copillar[5]arene Conjugates for Enhanced Nanodelivery: Synthesis, Nanoparticle Optimization, and In Vitro Biocompatibility.Macromolecular bioscience · 2026Article
- Engineered circular RNA compatible with complete nucleoside modification and rolling circle translation through a Cap-independent translation enhancer.Nature biomedical engineering · 2026Article
- Analytical Characterization and Stability Assessment of RNA-Based Vaccines.Pharmaceutics · 2026Review
- Efficacy and Safety of Messenger RNA Vaccines.Health science reports · 2026Article
- Nanoadjuvant-integrated organic biomaterials for immune engineering: Mechanisms, design strategies, and translational applications.Materials today. Bio · 2026Review
- The RNA delivery dilemma-lipid versus polymer nanoparticle platforms.Drug delivery and translational research · 2026Article
- Review
- Folic acid-modified antigen-trapping nanoprobes for developing in situ tumor vaccines to inhibit metastasis and recurrence of ovarian cancer.Journal of nanobiotechnology · 2026Article
- Delivery of mRNA Therapeutics Beyond Infectious Diseases: Design Innovations and Applications in Oncology, Cardiovascular, and Rare Genetic Diseases.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Thioester-Containing Ionizable Lipids with Enhanced Endosomal Escape and Biodegradability for mRNA and tRNA Delivery.Pharmaceutics · 2026Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To elicit optimal immune responses, messenger RNA vaccines require intracellular delivery of the mRNA and the careful use of adjuvants. Here we report a multiply adjuvanted mRNA vaccine consisting of lipid nanoparticles encapsulating an mRNA-encoded antigen, optimized for efficient mRNA delivery and for the enhanced activation of innate and adaptive responses. We optimized the vaccine by screening a library of 480 biodegradable ionizable lipids with headgroups adjuvanted with cyclic amines and by adjuvanting the mRNA-encoded antigen by fusing it with a natural adjuvant derived from the C3 complement protein. In mice, intramuscular or intranasal administration of nanoparticles with the lead ionizable lipid and with mRNA encoding for the fusion protein (either the spike protein or the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) increased the titres of antibodies against SARS-CoV-2 tenfold with respect to the vaccine encoding for the unadjuvanted antigen. Multiply adjuvanted mRNA vaccines may improve the efficacy, safety and ease of administration of mRNA-based immunization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.