Title:
Metal-Organic Frameworks for Long-term Vaccine Storage

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MURTY-DISSERTATION-2022.pdf (3.78 MB)
Author(s)
Murty, Rohan A.
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Prausnitz, Mark R.
 Walton, Krista S.
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School of Chemical and Biomolecular Engineering
School established in 1901 as the School of Chemical Engineering; in 2003, renamed School of Chemical and Biomolecular Engineering
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https://hdl.handle.net/1853/73022
Abstract
The long-term thermostabilizing effects of vaccine encapsulation within a metal-organic framework (MOF) were studied in this work. In the first research aim, tetanus toxoid (TT) vaccine was encapsulated within zeolitic imidazolate framework -8 (ZIF-8) to create the biocomposite material TT@ZIF, which was characterized by several spectroscopic, microscopic, and crystallographic methods (i.e., FTIR, SEM, CLSM, XRD). The thermostability of TT@ZIF in a variety of solid and liquid formulations was measured with ELISA as part of an accelerated stability study. The best stability results were obtained by suspending TT@ZIF crystallites in a propylene glycol mixture, and Arrhenius modeling suggested this formulation could meet several industrially-accepted vaccine stability guidelines for one year. Furthermore, a 4-week in vivo study of the immunogenic responses to TT@ZIF formulations was conducted in a murine model. In the second research aim, the protein bovine serum albumin (BSA) was encapsulated in two isostructural ZIFs and characterized by synchrotron source small-angle x-ray scattering (SAXS). These experiments demonstrated that the encapsulated BSA SAXS spectra could be calculated by scaled spectra subtraction of the pure ZIF material from the biocomposite (BSA@ZIF). This allowed SAXS analysis of still-encapsulated proteins, which showed that encapsulated BSA retained its folded, globular structure even when exposed to a normally denaturing temperature of 70˚C in situ. These findings could help combat the cold chain and increase vaccine access in the developing world, as well as inform the rational design of other MOF-encapsulated systems involving enzymes, live viruses, or mRNA.
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2022-12-13
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Dissertation
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