ArticleImmunity2021
Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses.
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Article in Immunity, 2021. 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 466 papers.
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466citing papers in PubMed
27.1field-weighted citation impact, top 1% of its field
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Who cites it
466 citing papers in PubMed, 677 citations in OpenAlex.
- Randomized trial of same- versus opposite-arm coadministration of inactivated influenza and SARS-CoV-2 mRNA vaccines.JCI insight · 2025Trial
- Cytokine co-presentation on targeted lipid nanoparticles enhances in vivo T cell engineering.Biomaterials · 2027Article
- Novel lipid nanoparticle in a mRNA cancer vaccine drives tumor control via type I IFNs and effector CD8Molecular therapy. Nucleic acids · 2026Article
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- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- IL7R mRNA therapy enhances antitumor T cell immunity and suppresses tumor growth in preclinical tumor models.Journal for immunotherapy of cancer · 2026Article
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
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- mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.Molecular biomedicine · 2026Review
- Computational Design of a Trivalent Multi-Epitope mRNA Vaccine Candidate Against Western, Eastern, and Venezuelan Equine Encephalitis Viruses.Pharmaceutical research · 2026Article
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- Evaluation of lipid nanoparticle adjuvants with different PEG lipid ratios and phospholipid modifications in non-human primates.Molecular therapy. Nucleic acids · 2026Article
- A boost for CAR T cell therapy.Nature materials · 2026Article
- Nanomaterial-mediated functional remodeling of antigen-presenting cells: A novel strategy to break tumor immune escape.Acta pharmaceutica Sinica. B · 2026Review
- Advancements of mRNA-lipid nanoparticle links to gene editing and immune responses.Journal, genetic engineering & biotechnology · 2026Review
- Nanomaterials-Based Immunotherapy for Atherosclerosis.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Epitope-Based Nipah Virus G and F Head-to-Head Dimer mRNA Vaccines Exhibit Distinct Immunogenicity and Immune Profiles.Vaccines · 2026Article
- Enhanced Humoral and Cellular Immune Responses Elicited by a Liposomal Subunit Vaccine Based onVeterinary sciences · 2026Article
- Pulmonary Delivery of Self-Amplifying RNA: Balancing Inflammation and Durable Transgene Expression.ACS nano · 2026Article
406 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
32 authors at 7 institutions in 4 countries.
Mohamad-Gabriel AlamehDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
István TombáczDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Emily BettiniDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Katlyn LedererDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Chutamath SittplangkoonCenter of Excellence in Vaccine Research and Development, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Joel R WilmoreDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Brian T GaudetteDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ousamah Y SolimanDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Matthew PineDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Philip HicksDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Tomaz B ManzoniDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
James J KnoxDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John L JohnsonDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dorottya LaczkóDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hiromi MuramatsuDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Benjamin DavisDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Wenzhao MengDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Aaron M RosenfeldDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Shirin StrohmeierDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Paulo J C LinAcuitas Therapeutics, Vancouver, BC, Canada.
Barbara L MuiAcuitas Therapeutics, Vancouver, BC, Canada.
Ying K TamAcuitas Therapeutics, Vancouver, BC, Canada.
Katalin KarikóDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA; BioNTech RNA Pharmaceuticals, Mainz, Germany.
Alain JacquetCenter of Excellence in Vaccine Research and Development, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Florian KrammerDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Paul BatesDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Michael P CancroDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Drew WeissmanDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Eline T Luning PrakDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
David AllmanDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Michela LocciDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: michela.locci@pennmedicine.upenn.edu.
Norbert PardiDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: pnorbert@pennmedicine.upenn.edu.
University of Pennsylvania · USAcuitas Therapeutics (Canada) · CAChulalongkorn University · THIcahn School of Medicine at Mount Sinai · USThomas Jefferson University · USBioNTech (Germany) · DEPenn Center for AIDS Research · US
Funding
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3MNonhuman primate studies for development of a prototype HIV vaccine that induces broadly neutralizing antibodiesUM1AI144371 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2025
$190.4M COLLABORATIVE INFLUENZA VACCINE INNOVATION CENTER: UNIVERSAL INFLUENZA VACCINE RESEARCH75N93019C00051 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KRAMMER, FLORIAN · 2019 to 2025
$105.4MTranscriptomics and Repertoire ProfilingP01AI106697 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Donna L. Farber · 2013 to 2026
$31.3MProject 4: Computational panbetaCoV immunogen designP01AI158571 · NIAID · DUKE UNIVERSITY · PI HENDERSON, RORY · 2021 to 2023
$28.0MProject 2: Current Good Manufacture Practices (CGMP) Production of Nucleoside-Modified mRNAs Encoding HIV-1 EnvelopesU19AI135902 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2018 to 2022
$19.8MProject 2 - GMP Manufacturing of mRNA ImmunogensU19AI142596 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2024
$19.0MIMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MProteasome Targeting for Alloreactive Plasma CellsR01AI154932 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ALLMAN, DAVID M, HILDEMAN, DAVID A · 2020 to 2025
$7.2MTRAINING IN VIROLOGYT32AI007324 · NIAID · WISTAR INSTITUTE · PI Paul Bates, Matthew D. Weitzman · 1989 to 2026
$6.8MLipid 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
$4.2MVMD-PhD Training in Infectious Disease-Related ResearchT32AI070077 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Michael Lee Atchison · 2008 to 2026
$3.5MNCI NIH HHS P30 CA016520NCI NIH HHS T32 CA009140NIAID NIH HHS 75N93019C00051NIAID NIH HHS P01 AI106697NIAID NIH HHS P01 AI158571NIAID NIH HHS R01 AI123738NIAID NIH HHS R01 AI124429NIAID NIH HHS R01 AI139123NIAID NIH HHS R01 AI146101NIAID NIH HHS R01 AI146420NIAID NIH HHS R01 AI152236NIAID NIH HHS R01 AI153064NIAID NIH HHS R01 AI154932NIAID NIH HHS R21 AI142638NIAID NIH HHS T32 AI007324NIAID NIH HHS T32 AI070077NIAID NIH HHS U19 AI135902NIAID NIH HHS U19 AI142596NIAID NIH HHS UM1 AI144371
Abstract
Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity that promotes induction of strong T follicular helper cell, germinal center B cell, long-lived plasma cell, and memory B cell responses that are associated with durable and protective antibodies in mice. Comparative experiments demonstrated that this LNP formulation outperformed a widely used MF59-like adjuvant, AddaVax. The adjuvant activity of the LNP relies on the ionizable lipid component and on IL-6 cytokine induction but not on MyD88- or MAVS-dependent sensing of LNPs. Our study identified LNPs as a versatile adjuvant that enhances the efficacy of traditional and next-generation vaccine platforms.
Indexed as
Adaptor Proteins, Signal TransducingAdjuvants, ImmunologicAnimalsB-LymphocytesCOVID-19COVID-19 VaccinesGerminal CenterHEK293 CellsHumansImmunity, HumoralInterleukin-6LiposomesMiceMice, Inbred BALB CmRNA VaccinesNanoparticlesAdaptor Proteins, Signal TransducingAdjuvants, ImmunologicCOVID-19 VaccinesInterleukin-6Lipid NanoparticlesLiposomesMAVS protein, mousemRNA VaccinesProtein Subunitsadjuvantgerminal centersIL-6influenza viruslipid nanoparticleSARS-CoV-2Tfh cellvaccine
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