Improving aerosolization and potency of a thermally stable spray dried vaccine platform for inhalation delivery
Bibliographic record
Abstract
Pulmonary immunization via inhalation of aerosolized vaccines offers enhanced immunity against respiratory diseases, in addition to the ability to mitigate cold-chain requirements. Achieving ideal particle size and consistent aerosolization of vaccine powders to achieve efficient lung deposition is challenging. In contrast to respiratory delivery of non-biological pharmaceuticals, there is no well characterized formulation platform readily adaptable to incorporating sensitive biologics like viruses and viral vectors. This work focuses on improving the aerosolization and bioactivity of spray dried vaccines to achieve the end goal of effective immunization via inhalation. The biologics studied in this work were human serotype 5 adenovirus (AdHu5) and Influenza H1N1 PR8 (influenza). First, eight amino acids, known to improve the dispersibility, were screened for improving aerosolization of adenovirus containing mannitol/dextran (control) powder. However, no amino acid significantly improved the aerosolization performance compared to the control, but the presence of amino acids was found to decrease the viral activity in dry powders. To understand the effect of amino acid concentration on aerosolization and underlying negative effects on adenovirus activity, L-leucine was chosen for further investigation due to its comparable aerosol performance to the control. While a high concentration of L-leucine (>50% (w/w)) improved the aerosolization significantly, it was found to cause aggregation of adenoviruses in liquid formulation prior to spray drying. Further, the factors underlying the activity losses of adenovirus in spray dried powders were explored. It was found that the presence of internal solid air interface within the microstructure of the dry particles are important indicators of activity losses in spray dried formulations. This work provides a deeper understanding of the previously unexplored causes of viral activity losses in liquid formulation (negative effects of amino acids on viruses) and dry particles (inactivation of viruses at solid air interfaces). Finally, a thermally stable dry powder vaccine platform with high aerosolization was developed for influenza vaccine and was tested for immunogenicity in mice. The work outlined the challenges associated with dry powder administration in murine models for preclinical studies and used a custom made dosator device. The final dry powder vaccine platform developed for influenza virus showed high aerosolization (>40% FPF) and elicited efficient immune response in mice. The dry powder formulation platform developed in this work can be explored for other vaccines. The knowledge gained from this work offers a major step forward in the development of marketable dry powder vaccines for inhalation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".