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Record W4417497881 · doi:10.1016/j.cell.2025.11.023

Distinct components of mRNA vaccines cooperate to instruct efficient germinal center responses

2025· article· en· W4417497881 on OpenAlexaff
Diana Castaño, Emily Bettini, Binod Kumar, Aleksey Chudnovskiy, Anna Siv, Giulia Protti, Sandra Nakadakari-Higa, Simona Ceglia, Nina De Luna, Joy E. Chiu, Katlyn Lederer, Shuk Hang Li, Hiromi Muramatsu, Thandiswa Mdluli, Edit Ábrahám, Sinem E. Sahingur, Ivan Maillard, Ying K. Tam, Sunny Shin, Scott E. Hensley, Jonathan J. Miner, Zoltán Lipinszki, Andrea Reboldi, Norbert Pardi, Roberto Spreafico, Gabriel D. Victora, Michela Locci

Bibliographic record

VenueCell · 2025
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunotherapy and Immune Responses
Canadian institutionsAcuitas Therapeutics (Canada)
FundersNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteNational Institutes of HealthNational Institute of Neurological Disorders and StrokeCharles A. King TrustMagyar Tudományos AkadémiaDamon Runyon Cancer Research FoundationAmerican Association of ImmunologistsHoward Hughes Medical Institute
KeywordsGerminal centerMessenger RNACellB cellAdjuvantRNAAntibodyCell type

Abstract

fetched live from OpenAlex

Nucleoside-modified messenger RNA (mRNA) vaccines elicit protective antibodies through their ability to promote T follicular helper (Tfh) cell differentiation. The lipid nanoparticles (LNPs) of mRNA vaccines possess inherent adjuvant activity. However, the extent to which the nucleoside-modified mRNA is sensed and contributes to Tfh cell responses remains undefined. Herein, we deconvolute the signals induced by LNPs and mRNA that instruct dendritic cells (DCs) to promote Tfh cell differentiation. We demonstrate that the mRNA drives the production of type I interferons, which act on DCs to enhance their maturation and Tfh cell differentiation, and favors plasma cells and memory B cell responses. In parallel, LNPs, which allow for mRNA uptake by DCs within the draining lymph node, also modulate Tfh cell responses by shaping the localization of CD25 + DCs. Our work unravels distinct adjuvant features of mRNA and LNPs necessary for the induction of Tfh cells, with implications for rational vaccine design.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.192
Threshold uncertainty score0.615

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.251
Teacher spread0.240 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations24
Published2025
Admission routes1
Has abstractyes

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