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Distinct components of nucleoside-modified messenger RNA vaccines cooperate to instruct efficient germinal center responses

GSE266931 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/10/09 Platform GPL24247
Summary
Nucleoside-modified mRNA vaccines elicit protective antibodies through their ability to promote T follicular helper (Tfh) cells. The lipid nanoparticle (LNP) component of mRNA vaccines possesses inherent adjuvant activity. However, to what extent the nucleoside-modified mRNA can be sensed and contribute to Tfh cell responses remains largely undefined. Herein, we deconvoluted the signals induced by LNP and mRNA that instruct dendritic cells (DCs) to promote Tfh cell differentiation. We demonstrated that the nucleoside-modified mRNA drives the production of type I interferons that act on DCs to induce their maturation and the induction of Th1-biased Tfh responses. Conversely, LNP favors the acquisition of a Tfh cell-inducing program in DCs, a stronger Th2 polarization in Tfh cells, and allows for rapid mRNA translation by DCs within the draining lymph node. Our work unravels distinct adjuvant features of mRNA and LNP necessary for the induction of Tfh cells, with implications for vaccine design.
Published in
Distinct components of mRNA vaccines cooperate to instruct efficient germinal center responses
Castaño D, Bettini E, Kumar B et al. · Cell 2025 · PMID 41406961 · doi:10.1016/j.cell.2025.11.023
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Also filed as BioProject PRJNA1108732 and SRA study SRP506201. Searching any of these in the dataset finder brings you back here.

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