Protective CD8 T Cell–Mediated Immunity against Influenza A Virus Infection following Influenza Virus–like Particle Vaccination
Bibliographic record
Abstract
The development of influenza A virus (IAV) vaccines capable of inducing cytotoxic CD8 T cell responses could potentially provide superior, long-term protection against multiple, heterologous strains of IAV. Although prior studies demonstrated the effectiveness of baculovirus-derived virus-like particle (VLP) vaccination in generating Ab-mediated protection, the role that CD8 T cell immunity plays in overall VLP-mediated protection is less-well understood. In this article, we demonstrate that intranasal vaccination of mice with a VLP containing the hemagglutinin and matrix 1 proteins of IAV/PR/8/34 leads to a significant increase in hemagglutinin 533-specific CD8 T cells in the lungs and protection following subsequent homologous challenge with IAV. VLP-mediated protection was significantly reduced by CD8 T cell depletion, indicating a critical role for CD8 T cells in protective immunity. Importantly, our results show that VLP vaccine-induced CD8 T cell-mediated protection is not limited to homologous IAV strains. VLP vaccination leads to an increase in protection following heterosubtypic challenge with a strain of IAV that avoids vaccine-induced neutralizing Abs but contains conserved, immunodominant CD8 T cell epitopes. Overall, our results demonstrate the ability of influenza protein-containing VLPs to prime IAV-specific CD8 T cell responses that contribute to protection from homo- and heterosubtypic IAV infections. These results further suggest that vaccination strategies focused on the development of cross-protective CD8 T cell responses may contribute to the development of "universal" IAV vaccines.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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".