Thermal stability of spray dried vaccine powders encapsulating enveloped and non-enveloped viral vectors
Bibliographic record
Abstract
This thesis work aims to improve the thermal stability of vesicular stomatitis virus (VSV) through spray drying and investigates differences in thermal stability in a matrix between enveloped and non-enveloped viral vectors. The spray drying process was used to dry and encapsulate the VSV vector within the glassy amorphous phase of a matrix of carbohydrate excipients, which imparted increased thermal stability. Viral activity was maintained when the powders were stored for 30 days at 37 °C, in contrast to the liquid control that lost all activity after 15 days. The best excipients for enhancing thermal stability of VSV were trehalose and a 3:1 blend of trehalose and dextran. Immunogenic response from the spray dried trehalose-VSV particles was detected through an in vivo study with Female BALB/c mice after storing the vaccine for 15 days at 37 °C. Two enveloped viral vectors, VSV and influenza, and a non-enveloped viral vector, human type 5 adenoviral vector (AdHu5) were spray dried with the same formulations to observe how excipients enhance thermal stability and encapsulate the different groups of viruses. The thermal stability of both enveloped viral vectors was enhanced the most when spray dried with trehalose or a 3:1 trehalose/dextran blend, and exhibited the greatest activity loss when spray dried with a mannitol/dextran blend, determined by in vitro TCID50 assays measuring GFP expression. Conversely, the best performing excipient formulation for the non-enveloped viral vector was a mannitol/dextran blend. This led to the hypothesis that the encapsulation mechanism differs between the two groups of viruses. The glass transition temperature (Tg) of the spray dried formulations (without virus) stored at 37 °C for 10 days was measured to infer the potential molecular mobility of the viral vector within the primarily amorphous matrix. Formulations containing dextran exhibited the smallest depression in Tg after storage, indicating minimal increase in molecular mobility over time. RNA leakage from aged spray dried powders containing VSV was quantified to investigate the encapsulation mechanism of enveloped viral vectors and followed a similar trend to the in vitro activity tests. VSV with poor performing excipients yielded the least detectable RNA/pfu after three days of storage at 45°C, suggesting that the lipid envelopes ruptured and released viral RNA which denatured during storage. This work demonstrates that the VSV vector can be thermally stabilized through spray drying but highlights that different carbohydrates interact differently with enveloped versus non-enveloped viral vectors, providing a guideline for future work with the advent of new vaccines.
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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".