Evidence map›Paper›PMID 34841223›Full record

ArticleiScience2021

The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory.

Sonia Ndeupen, Zhen Qin, Sonya Jacobsen, Aurélie Bouteau, Henri Estanbouli, Botond Z Igyártó

Open access · goldAbstract read
In one paragraph

Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 381 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
381citing papers in PubMed, 1 pooled it
30.1field-weighted citation impact, top 1% of its field
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

381 citing papers in PubMed, 1 synthesis or guideline pooled it, 581 citations in OpenAlex.

  1. Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025
    Pooled it
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  4. Development of mRNA vaccines against herpes zoster.Human vaccines & immunotherapeutics · 2026
    Review
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  7. RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026
    Review
  8. Article
  9. Therapeutic vaccines for NSCLC: From mechanisms to clinical translation.Chinese medical journal pulmonary and critical care medicine · 2026
    Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. mRNA Vaccines for Influenza: Hope for a Universal Vaccine?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review

321 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Sonia NdeupenDepartment of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA.
Zhen QinDepartment of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA.
Sonya JacobsenDepartment of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA.
Aurélie BouteauDepartment of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA.
Henri EstanbouliDepartment of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA.
Botond Z IgyártóDepartment of Microbiology and Immunology, Thomas Jefferson University, Philadelphia 19107 PA, USA.
Thomas Jefferson University · US

Funding

DC-subset-tailored vaccinesR01AI146420 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI IGYARTO, BOTOND Z · 2020 to 2024
$1.9M
NIAID NIH HHS R01 AI146420
6 · The paper itself

Abstract

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature.

Indexed as

Biological sciencesBiotechnologyImmunology

Identifiers

PMID34841223
PMCPMC8604799
OpenAlexW3217355073

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.