The roles of CD4+ T cell help, sex, and dose in the induction of protective CD8+ T cells against a lethal poxvirus by mRNA-LNP vaccines
Bibliographic record
Abstract
The role of CD4<sup>+</sup> T cells in the induction of protective CD8<sup>+</sup> T cells by mRNA lipid nanoparticle (LNP) vaccines is unknown. We used B6 or <i>Tlr9</i><sup>−/−</sup> mice depleted or not of CD4<sup>+</sup> T cells and LNP vaccines loaded with mRNAs encoding the ectromelia virus (ECTV) MHC class I H-2 K<sup>b</sup>-restricted immunodominant CD8<sup>+</sup> T cell epitope TSYKFESV (TSYKFESV mRNA-LNPs) or the ECTV EVM158 protein, which contains TSYKFESV (EVM-158 mRNA-LNPs). Following prime and boost with 10 μg of either vaccine, K<sup>b</sup>-TSYKFESV-specific CD8<sup>+</sup> T cells fully protected male and female mice from ECTV at 29 (both mRNA-LNPs) or 90 days (EVM158 mRNA-LNPs) post boost (dpb) independently of CD4<sup>+</sup> T cells. However, at 29 dpb with 1 μg mRNA-LNPs, males had lower frequencies of K<sup>b</sup>-TSYKFESV-specific CD8<sup>+</sup> T cells and were much less well protected than females from ECTV, also independently of CD4<sup>+</sup> T cells. At 90 dpb with 1 μg EVM158 mRNA-LNPs, the frequencies of K<sup>b</sup>-TSYKFESV-specific CD8<sup>+</sup> T cells in males and females were similar, and both were similarly partially protected from ECTV, independently of CD4<sup>+</sup> T cells. Therefore, at optimal or suboptimal doses of mRNA-LNP vaccines, CD4<sup>+</sup> T cell help is unnecessary to induce protective anti-poxvirus CD8<sup>+</sup> T cells specific to a dominant epitope. At suboptimal doses, protection of males requires more time to develop.
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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 | 0.001 | 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 | 0.001 |
| 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".