Development and characterization of thermostable thin films as a novel vaccine dosage form

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dc.contributor.advisorCroyle, Maria A.
dc.contributor.committeeMemberSmyth, Hugh D
dc.contributor.committeeMemberGhosh, Debadyuti
dc.contributor.committeeMemberMaynard, Jennifer A
dc.contributor.committeeMemberMiddaugh, Charles R
dc.creatorBajrovic, Irnela
dc.creator.orcid0000-0002-5066-2673
dc.date.accessioned2021-05-24T20:40:44Z
dc.date.available2021-05-24T20:40:44Z
dc.date.created2020-12
dc.date.issued2020-12-09
dc.date.submittedDecember 2020
dc.date.updated2021-05-24T20:40:45Z
dc.description.abstractThermostabilization of vaccines can significantly simplify vaccine storage and distribution processes, eliminating the need for cold-chain maintenance, and resulting in global access to life-saving vaccines. Despite this benefit, all approved vaccines for use by the Food and Drug Administration must be refrigerated for long term storage in order to guarantee potency. The first study described in this thesis demonstrated that formulation of live adenovirus in the novel thin film matrix protects the virus from degradation at 4°C and 20°C for a minimum of three months, as well as 14 days at 37°C and 5 days at 40°C. The film matrix protected virus through 16 freeze-thaw cycles as well. As formulations prepared with surfactant outperformed those without it, the second study was designed to characterize and evaluate the intermolecular interactions between the surfactant and adenovirus capsids. in order to better understand the surfactants contribution to stability. The data suggested that surfactant stabilizes adenovirus by preventing aggregation of capsids via electrostatic and hydrophobic interactions. Additionally, the other formulation components in our multi-component preparation mitigates the interactions between adenovirus and the surfactant without interfering with stability. Lastly, the principles of surfactant stabilization were applied to the identification of alternative excipients for stabilization of a virus with different properties from adenovirus, H1N1 influenza. The third study evaluated the ability of the thin film platform to induce an immune response and the impact of a natural adjuvants on the cytokine response and bioavailability of the vaccine dose. A preliminary screen demonstrated that vaccination with the thin film platform resulted in a stronger humoral response following mucosal vaccination than with traditional intramuscular vaccination. Additionally, the optimized formulation improved bioavailability of the viral dose across human buccal explants. Further characterization of the immune response also revealed that sublingual routes induced a strong TH1 polarized immune response which resulted in greater protective efficacy than intramuscular immunization. Taken together, these studies identified a novel thin film platform capable of stabilizing adenovirus at ambient temperatures, provide key insights into viral stabilization in the novel thin film platform, and illustrate the utility of the thin film as mucosal vaccine dosage form.
dc.description.departmentPharmaceutical Scienceseng
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/2152/86218
dc.identifier.urihttp://dx.doi.org/10.26153/tsw/13169
dc.language.isoen
dc.subjectVaccine
dc.subjectThermostable
dc.subjectOral mucosa
dc.titleDevelopment and characterization of thermostable thin films as a novel vaccine dosage form
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentPharmaceutical Sciences
thesis.degree.disciplinePharmaceutical Sciences
thesis.degree.grantorThe University of Texas at Austin
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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