Evidence map›Paper›PMID 41566773›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

Inflammatory mediators of mRNA vaccine-induced adverse reactions in mice.

Koyo Honda, Tatsuya Karaki, Yuta Kunishima, Yoshino Kawaguchi, Naoki Takemura, Takashi Matsuzaki, So-Ichiro Fukada, Tatsuya Saitoh, Toshiro Hirai, Yasuo Yoshioka

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
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

10 authors.

Koyo HondaLaboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tatsuya KarakiVaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; The Research Foundation for Microbial Diseases of Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yuta KunishimaVaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; The Research Foundation for Microbial Diseases of Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yoshino KawaguchiVaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Naoki TakemuraLaboratory of Bioresponse Regulation, Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Takashi MatsuzakiDepartment of DDS Pharmaceutical Development, Graduate School of Medicine, The University of Osaka, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Center for Advanced Modalities and DDS, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
So-Ichiro FukadaLaboratory of Stem Cell Regeneration and Adaptation, Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tatsuya SaitohLaboratory of Bioresponse Regulation, Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Center for Infectious Disease Education and Research, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Global Center for Medical Engineering and Informatics, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Toshiro HiraiLaboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Center for Advanced Modalities and DDS, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yasuo YoshiokaLaboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; The Research Foundation for Microbial Diseases of Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Center for Advanced Modalities and DDS, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Center for Infectious Disease Education and Research, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Global Center for Medical Engineering and Informatics, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: y-yoshioka@biken.osaka-u.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

mRNA vaccines are promising vaccine modalities against infectious diseases. However, these vaccines frequently cause adverse reactions, such as fever and fatigue, which are exacerbated after a booster dose, leading to vaccine hesitancy. Here, we elucidated the mechanisms underlying adverse reactions in mice after prime and boost vaccinations with mRNA vaccines. The mRNA vaccine induced systemic adverse reactions, such as fever, and local adverse reactions, such as enhanced vascular permeability, at the vaccination site in mice. Lipid nanoparticles (LNPs) used for mRNA encapsulation mainly contributed to these adverse reactions. We identified IL-1, IL-6, TNF-α, and type 1 IFN as key cytokines and COX-2 and PGE2 as inflammatory mediators responsible for systemic adverse reactions. TNF-α levels were enhanced after the boost vaccination by IFN-γ secreted from prime-vaccination-induced T cells, contributing to systemic adverse reactions. In addition, local adverse reactions at the vaccination site were caused by a mechanism different from that of systemic adverse reactions. We also found that the inhibition of IL-6 effectively reduced the adverse reactions while maintaining the vaccine effects. These data provide basic information for understanding adverse reactions in humans and may be useful for developing mRNA vaccines with fewer adverse reactions.

Indexed as

Inflammation MediatorsmRNA VaccinesRNA, MessengerAnimalsCyclooxygenase 2CytokinesDinoprostoneFemaleInterleukin-6LiposomesMiceNanoparticlesTumor Necrosis Factor-alphaVaccinationCyclooxygenase 2CytokinesDinoprostoneInflammation MediatorsInterleukin-6Lipid NanoparticlesLiposomesmRNA VaccinesRNA, MessengerTumor Necrosis Factor-alphaadverse reactionscytokinesfeverIL-6lipid nanoparticlemRNA vaccine

Identifiers

PMID41566773
PMCPMC13069329

What OpenQuestion holds

Textmetadata
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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.