Modulation of mucosal immunity and tissue resident memory formation by NS1-deficient influenza A virus
Bibliographic record
Abstract
Abstract Recurrent influenza A virus (IAV) epidemics and occasional pandemics as a result of viral genome reassortment and human adaptation pose significant health burdens globally. The non-structural protein 1 (NS1) mediates attenuation of host response and facilitates viral replication in the nucleus. While intranasal vaccination using NS1-deleted live attenuated virus has been shown to induce pulmonary mucosal immunity in animal models, the immunological details have not been fully studied. In vivo mouse infection using wild type (WSN/WT) and NS1-deleted WSN (WSN/Del) showed WSN/Del induced massive type I interferon response in murine lungs, whereas pulmonary inflammation was minimal. Skewed migration of CD103+ dendritic cells (DC) to mediastinal lymph nodes upon WSN/Del infection was observed with enhanced formation and persistence of tissue resident influenza-specific memory CD8 T cells (TRM). After rechallenge, while influenza-specific TRM in both groups expanded comparably, more polyfunctionality was seen in TRM from WSN/Del immunized mice than WSN/WT recovered mice. Single cell RNA-seq of migratory DC in initial immunization showed differential gene programs associated with WSN/Del infection. Ongoing work is undertaken to identify the signals provided by DC that may lead to preferential priming of T cells to tissue resident lineage. Since TRM have been illustrated to confer heterosubtypic protection, knowledge on the specific physiological cues that facilitate TRM formation and retention will be useful to vaccine development.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".