Topical TLR9 agonists induce more efficient cross‐presentation of injected protein antigen than parenteral TLR9 agonists do
Bibliographic record
Abstract
Topical application of adjuvant to the skin promotes the generation of immune responses to co-administered peptide or protein antigen. We demonstrate that topical administration of CpG adjuvant (a TLR9 agonist) induces the cross-presentation of, and antigen-specific CTL induction to, locally injected soluble protein antigen. C57BL/6 mice were immunized by subcutaneous or intramuscular injection with ovalbumin (OVA) protein as model antigen. Application of CpG to the local skin induced more efficient cross-presentation of the injected antigen than co-injected adjuvant. Robust antigen-specific CTL responses were generated, as determined by antigen-specific CTL enumeration using tetramers, IFN-gamma ELISPOT analysis and cytotoxicity assays. Long-term memory CTL responses were induced. Topical administration of adjuvant induced Langerhans cell migration, local type 1 IFN-dependent myxovirus-resistance protein A expression and bystander dendritic cell (DC) activation. Soluble antigen-bearing DC within the skin draining lymph nodes were mainly CD11chiCD11bhilangerinloDEC205lo. Topical administration did not result in the splenomegaly or systemic cytokine induction (including TNF-alpha, IL-12, IFN-gamma and MCP-1) noted with parenteral administration. Topical TLR9 family agonists may be used to modulate the immune response to soluble protein vaccines administered by standard percutaneous route. Topical adjuvant administration increases efficacy of CTL induction and reduces toxicity when compared to parenteral adjuvant administration.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".