Evidence map›Paper›PMID 41991944›Full record

ArticleNPJ vaccines2026

A poorly reactogenic lipid nanoparticle-mRNA vaccine unveils an innate immune pathway for adverse reactions.

Tomohiro Takano, Keigo Kumagai, Hitoshi Iuchi, Kazutaka Terahara, Aya Mizuike, Eita Sasaki, Yu Adachi, Ryutaro Kotaki, Saya Moriyama, Shinichiro Ota and 14 more

Abstract read
In one paragraph

Article in NPJ vaccines, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

24 authors.

Tomohiro TakanoResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Keigo KumagaiDepartment of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Hitoshi IuchiFaculty of Science and Engineering, Waseda University, Tokyo, Japan.
Kazutaka TeraharaResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Aya MizuikeDepartment of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Eita SasakiResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Yu AdachiResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Ryutaro KotakiResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Saya MoriyamaResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Shinichiro OtaRespiratory Disease Center, Tokyo Shinagawa Hospital, Tokyo, Japan.
Mizuki FujisawaResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Tomoharu MizukamiDepartment of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Kyoko SaitoDepartment of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Masanori IsogawaResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Kohei SogaResearch Center for Food Safety, The University of Tokyo, Tokyo, Japan.
Haruyo Nakajima-AdachiResearch Center for Food Safety, The University of Tokyo, Tokyo, Japan.
Satoshi HachimuraResearch Center for Food Safety, The University of Tokyo, Tokyo, Japan.
Kouji KobiyamaDivision of Vaccine Science, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Ken J IshiiDivision of Vaccine Science, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Michiaki HamadaFaculty of Science and Engineering, Waseda University, Tokyo, Japan.
Masayoshi FukasawaDepartment of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
Masaharu ShinkaiRespiratory Disease Center, Tokyo Shinagawa Hospital, Tokyo, Japan. shinkai050169@gmail.com.
Takayuki MatsumuraResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. matsumura.t@jihs.go.jp.
Yoshimasa TakahashiResearch Center for Vaccine Development, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. takahashi.yos@jihs.go.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipid nanoparticle (LNP)-mRNA vaccines robustly activate immune responses, contributing to their high efficacy and frequent adverse reactions (ARs). Here, we identified an LNP-mRNA formulation with a more favorable balanced immunogenicity-reactogenicity profile. Immune profiling in a mouse model defined the reactogenic LNP-mRNA vaccine as a potent inducer of HMGB1 release, pro-inflammatory cytokine production, and concurrent neutrophil infiltration. HMGB1 induced TNF-α secretion from monocyte subsets, yet in vivo blockade studies revealed the contribution of multiple cytokines (TNF-α, IL-1, and IL-6) to reactogenicity. Among the reactogenic cytokines, IL-1 was identified as the key mediator of vaccine-induced ARs, but was dispensable for humoral immunity. The clinical relevance was confirmed in a well-controlled vaccine cohort where IL-1 pathway activation correlated with fever severity but not with neutralizing antibody titers. We dissected early innate pathways specifically linked to vaccine reactogenicity, providing a rationale for selectively reducing ARs in next-generation vaccines.

Identifiers

PMID41991944
PMCPMC13323985

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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.