Distinct components of mRNA vaccines cooperate to instruct efficient germinal center responses
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".