ArticleNature nanotechnology2025
Tailoring the adjuvanticity of lipid nanoparticles by PEG lipid ratio and phospholipid modifications.
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Article in Nature nanotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23citing papers in PubMed
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Who cites it
23 citing papers in PubMed.
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.Molecular biomedicine · 2026Review
- Dual pKa Lipid Nanoparticles for Lung-tropic mRNA Delivery and pH-Programmed Endosomal Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Breast cancer prevention by prophylactic Lalba mRNA-LNP vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Evaluation of lipid nanoparticle adjuvants with different PEG lipid ratios and phospholipid modifications in non-human primates.Molecular therapy. Nucleic acids · 2026Article
- Assembly delivery of bioactive matters: Advances, challenges, and prospects.Journal of advanced research · 2026Review
- Nanomaterials-Based Immunotherapy for Atherosclerosis.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Defining Composition-Cytokine Relationships Enables the Design of Lipid Nanoparticles with Programmed Immunogenicity.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Influenza B mosaic HA mRNA-LNP vaccines are cross-reactive and protective in mice.Molecular therapy. Nucleic acids · 2026Article
- Nanoadjuvant-integrated organic biomaterials for immune engineering: Mechanisms, design strategies, and translational applications.Materials today. Bio · 2026Review
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Engineering a safe and potent LNP-mRNA delivery system by leveraging the dual activities of α-tocopherol.International journal of pharmaceutics: X · 2026Article
- Review
- Programmable lipid nanoparticles for RNA therapeutics: Design principles and clinical translation.Materials today. Bio · 2026Review
- Combining Anti-Inflammatory Drugs and Cell-Specific Expression-Suppression Reduces the Adjuvant Activity of mRNA-LNPs.Molecular pharmaceutics · 2026Article
- Polymer-lipid hybrid nanoparticle enhances mRNA delivery and T cell-mediated immunity.bioRxiv : the preprint server for biology · 2026Article
- Optimal murine CD4Nature communications · 2026Article
- Preclinical evaluation of an mRNA-LNPs vaccine for mucosal protection against dental caries.Frontiers in microbiology · 2026Article
- Distinct components of mRNA vaccines cooperate to instruct efficient germinal center responses.Cell · 2025Article
- Lipid nanoparticle-based mRNA platforms for mucosal HIV vaccines: formulation advances, immune mechanisms, and translational pathways.Archives of microbiology · 2025Review
Corrections and comments
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Authors and funding
35 authors.
Máté Vadovics *Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-9028-987X
Wenchen Zhao *Genevant Sciences Corporation, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0003-4450-6292
Emily F Daley *Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0008-2956-4156
Kieu LamGenevant Sciences Corporation, Vancouver, British Columbia, Canada.
Owen DalyGenevant Sciences Corporation, Vancouver, British Columbia, Canada.
Khalid RashidDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Hailey R LeeDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Petra SchreinerGenevant Sciences Corporation, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-8952-4748
Kendall A LundgreenDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2431-7152
Brian T GaudetteThe Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-6627-3085
Vladimir V ShuvaevDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2449-460X
Evguenia ArguiriDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hiromi MuramatsuDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-1544-1493
András SárközyDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Thandiswa MdluliDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Junchao XuDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0725-8111
Xuexiang HanDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0011-5222
Nina De LunaDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Diana CastañoDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5697-5603
Emily BettiniDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Edit ÁbrahámSynthetic and Systems Biology Unit, Institute of Biochemistry, HUN-REN Biological Research Centre, Szeged, Hungary.ORCID http://orcid.org/0000-0002-1268-760X
Zoltan LipinszkiSynthetic and Systems Biology Unit, Institute of Biochemistry, HUN-REN Biological Research Centre, Szeged, Hungary.ORCID http://orcid.org/0000-0002-2067-0832
Giuseppe CarlucciDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Avinash Haridas BansodeDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Katelyn NguyenDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Thuc M LeDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2364-9374
Tony LuuDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID http://orcid.org/0009-0003-1014-9300
Vladimir R MuzykantovDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Paul BatesDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3918-5976
David AllmanThe Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Michael J MitchellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3628-2244
Michela LocciDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Caius G RaduDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-9338-5397
James HeyesGenevant Sciences Corporation, Vancouver, British Columbia, Canada.
Norbert PardiDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. pnorbert@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0003-1008-6242
Funding
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3MVirus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ronald G Collman · 1999 to 2026
$78.6MTranslational Immunology CoreU19AI181968 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI FELGNER, PHILIP LOUIS · 2024 to 2024
$33.1MProject 4: Computational panbetaCoV immunogen designP01AI158571 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2021 to 2023
$28.0MUCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3MLipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responsesR01AI153064 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Michela Locci, Norbert Pardi · 2020 to 2026
$4.2MDevelopment of Universal Influenza Virus Vaccines Using Nucleoside-Modified Messenger RNAR01AI146101 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI PARDI, NORBERT · 2019 to 2023
$3.1MVascular Targeting of Nanocarriers for RNAR01HL155106 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R, WEISSMAN, DREW · 2021 to 2024
$3.1MInnovative mRNA vaccines to enhance the efficacy of T-cell transfer therapies against solid tumorsR01CA283736 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Norbert Pardi, Caius Gabriel Radu · 2024 to 2026
$3.1MDevelopment of vaccines targeting a tick-borne phlebovirusR01AI152236 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BATES, PAUL · 2020 to 2024
$3.0MCauses and Consequences of Adenosine Signaling in Pancreatic CancerR01CA290888 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Timothy R Donahue, Caius Gabriel Radu · 2024 to 2026
$2.0MNCI NIH HHS P30 CA016520NCI NIH HHS R01 CA283736NCI NIH HHS R01 CA290888NCI NIH HHS T32 CA009120NHLBI NIH HHS R01 HL155106NIAID NIH HHS P01 AI158571NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI146101NIAID NIH HHS R01 AI152236NIAID NIH HHS R01 AI153064NIAID NIH HHS U19 AI181968U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) P01AI158571U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI146101U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI153064
Abstract
Lipid nanoparticles (LNPs) represent the leading delivery platform for mRNA vaccines with advantageous biocompatibility, scalability, adjuvant activity and often an acceptable safety profile. Here we investigate the physicochemical characteristics and adjuvanticity of four-component LNPs. Previous vaccine studies have demonstrated that altering the ionizable lipid influences the adjuvanticity of an LNP; however, the impact of the polyethylene glycol lipid and phospholipid has received less attention. Our mRNA-LNP vaccine formulations utilized different phospholipids and varying ratios of polyethylene glycol lipid, whereas the ionizable lipid and cholesterol remained approximately constant. We demonstrate that such modifications impact the magnitude and quality of the vaccine-elicited immune responses. We also dissect the underlying mechanisms and show that the biodistribution and cellular uptake of LNPs correlate with the magnitude and quality of the immune responses. These findings support the rational design of novel LNPs to tailor immune responses (cellular or humoral focused) based on the vaccine application.
Indexed as
Adjuvants, ImmunologicLipidsNanoparticlesPhospholipidsPolyethylene GlycolsAnimalsFemaleLiposomesMiceMice, Inbred C57BLTissue DistributionAdjuvants, ImmunologicLipid NanoparticlesLipidsLiposomesPhospholipidsPolyethylene Glycols
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