Development of Exclusive and Efficient Intranasal or Pulmonary Dosing Methods for a Dry Powder Tuberculosis Vaccine for Use in Nonhuman Primates
Bibliographic record
Abstract
Background: In spite of efforts to eradicate tuberculosis (TB), TB remains the deadliest infectious disease in the world; there is an urgent need for a thermostable, noninvasive TB vaccine suitable for distribution in the developing world. Spray-dried versions of a clinical-stage TB vaccine, ID93 + GLA-SE, are currently undergoing testing in baboons in both pulmonary and intranasal versions. We developed manufacturing processes and delivery systems to achieve delivery of each version to its intended site of action while avoiding off-target deposition. Methods: Pulmonary ID93 + GLA-SE was manufactured in a custom research-scale spray dryer. Delivery efficiency using a custom intratracheal insufflator was measured gravimetrically, and aerodynamic performance was evaluated via cascade impaction. Intranasal ID93 + GLA-SE was manufactured in a pilot-scale spray dryer. In vitro regional deposition in the Alberta Idealized Nasal Inlet, measured by LC-MS/MS, was used as a surrogate for aerodynamic performance; total deposition was used to calculate a total delivered dose. For both powders, ID93 antigen content was assessed using sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and GLA-SE adjuvant content was assessed via HPLC. Results: No substantial processing losses of the antigen or adjuvant were observed after spray drying in either formulation. For the pulmonary powder, the emitted dose exiting the endotracheal tube across three tube sizes ranged from 15.9% to 21.4% of the nominal dose; for the 8 mm tube size, the emitted dose mass median aerodynamic diameter was 5.3 µm, which was deemed suitable for pulmonary administration. For the intranasal powder, the delivered dose was 88% ± 2% of nominal, and in vitro deposition in the posterior nasal cavity was 63% ± 10% of the emitted dose, with minimal anticipated lung deposition. Conclusions: Pulmonary and intranasal spray-dried ID93 + GLA-SE powders were successfully manufactured. The proposed dosing systems are expected to achieve exclusive pulmonary or intranasal delivery to nonhuman primates while requiring only a moderate amount of powder.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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".