Evidence map›Paper›PMID 40246950›Full record

ArticleNPJ vaccines2025

Ionizable lipid nanoparticles of mRNA vaccines elicit NF-κB and IRF responses through toll-like receptor 4.

Amanda E Zelkoski, Zhongyan Lu, Gauthaman Sukumar, Clifton Dalgard, Hooda Said, Mohamad-Gabriel Alameh, Edward Mitre, Allison M W Malloy

Abstract read
In one paragraph

Article in NPJ vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed.

  1. Review
  2. Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  17. Article
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Amanda E ZelkoskiDepartment of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, MD, USA.
Zhongyan LuDepartment of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, MD, USA.
Gauthaman SukumarHenry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Clifton DalgardDepartment of Anatomy, Physiology & Genetics, Uniformed Services University of Health Sciences, Bethesda, MD, USA.
Hooda SaidDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Mohamad-Gabriel AlamehDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5672-6930
Edward MitreDepartment of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, PA, USA.ORCID http://orcid.org/0000-0001-7506-3266
Allison M W MalloyDepartment of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, MD, USA. allison.malloy@usuhs.edu.ORCID http://orcid.org/0000-0003-2962-0302

Funding

United States Department of Defense | Uniformed Services University of the Health Sciences (Uniformed Services University) RAMPU.S. Department of Defense (United States Department of Defense) HU00011920111U.S. Department of Defense (United States Department of Defense) HU00012020067U.S. Department of Defense (United States Department of Defense) HU00012120094U.S. Department of Defense (United States Department of Defense) HU00012120104
6 · The paper itself

Abstract

Ionizable lipid nanoparticles (LNP) that have enabled the success of messenger RNA (mRNA) vaccines have been shown to be immunostimulatory in the absence of mRNA. However, the mechanisms through which they activate innate immune cells is incompletely understood. Using a monocyte cell line, we compared the ability of three LNP formulations to activate transcription factors Nuclear Factor-kappa B (NF-κB) and Interferon Regulatory Factor (IRF). Comparison of signaling in knockout cell lines illustrated a role for Toll-like receptor (TLR) 4 in initiation of this signaling cascade and the contribution of the ionizable lipid component. Activation induced by empty LNPs was similar to that induced by LNPs containing mRNA, indicating that LNPs may provide the majority of innate stimulation for the mRNA vaccine platform. Our findings demonstrate that ionizable lipids within LNPs signal through TLR4 to activate NF-κB and IRF, identifying a mechanism for innate activation that can be optimized for adjuvant design.

Identifiers

PMID40246950
PMCPMC12006303

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.