Influence of L-leucine as a dispersibility enhancer on inhalation performance and immunogenicity of a dry powder influenza vaccine
Bibliographic record
Abstract
Developing dry powder formulations for sensitive biologics such as viral vaccines is not straightforward, with major challenges associated with their aerosolization still to be resolved, though their resulting tolerance for high temperatures makes these biopharmaceuticals easier to stockpile and transport. L-leucine is a known dispersibility enhancer for spray dried food and drug products that may improve the aerosolization of these new vaccines as well, but its full impact has not yet been studied across the supply chain from powder production to administration into a host for the viral actives being encapsulated. To establish better guidelines for formulators with L-leucine as a dispersibility enhancer in spray dried vaccine formulations, the whole supply chain was evaluated from dry powder synthesis and product stability, to aerosolization and delivery into the lungs, and finally whether the immunogenic response of the viral vector in murine models. An enveloped virus, Influenza A virus (IAV) was the targeted model viral vector for the study, stabilized in a binary matrix blend of lactose and trehalose, with and without L-leucine. Appropriately respirable particles (<5 μm) were produced, displaying aerodynamic properties sufficient for insufflation into mice via a custom-made intratracheal delivery device. In vivo immunogenicity was confirmed using a hemagglutination inhibition assay, with the spray dried powders inducing hemagglutinin inhibition (HAI) titers at protective levels. Though concerns were raised with L-leucine in deactivating a percentage of the virus in this study, the overall performance of the dry powder influenza vaccine benefited from its inclusion in the formulation. • L-leucine as a dispersibility enhancer showed positive role in aerosolization. • L-leucine showed no negative impact on viral activity, at 13 % concentration. • Demonstrated in vivo immunogenicity of dry powder with L-leucine.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| 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".