Year: 2024
Type: dissertation
Abstract: Two major barriers that impede equitable vaccine distribution are limited thermal stability of vaccines and the requirement to administer multiple doses of a vaccine to achieve a lasting immune response. Spray-drying and lyophilization can be used to embed vaccines in dry formulations with low residual water contents to improve the stability of the vaccine. Additionally, spray-dried vaccines can be coated with nanoscopic alumina layers via atomic layer deposition to enable controlled-release vaccine formulations. In this work, we developed dry formulations for different vaccine antigens and other complex therapeutics via spray-drying and lyophilization. These formulations typically conferred enhanced thermal stability to these antigens. Furthermore, we used atomic layer deposition to develop controlled-release vaccines and therapies using a range of antigens. To do this, we first aimed to understand what sources of stress might degrade antigens during formulation and drying processes. Next, we embedded a range of viral vectors in glassy formulations via spray-drying and lyophilization. We characterized these dry formulations and demonstrated that in the glassy state, viral vectors showed enhanced thermal stability compared to traditional liquid formulations. Additionally, we used atomic layer deposition to formulate two model viruses in alumina-coated particles for different controlled-release applications. We extended this work to other types of vaccines including protein-adjuvant vaccines and mRNA vaccines. We similarly characterized these vaccines and demonstrated that drying yielded vaccines with enhanced thermal stability. Additionally, we were able to use these techniques to formulate single-administration multi-dose vaccines to recapitulate HIV vaccine dosing schemes that have been shown to improve the immune response against HIV. Next, we evaluated spray-drying as a technique to reduce stringent cold-chain requirements of mRNA vaccines. In this work, we showed that mechanisms that destabilize mRNA vaccines in liquid formulations might differ from mechanisms that destabilize mRNA vaccines in glassy formulations. This will be critical to understand to stabilize. Finally, we demonstrated that this platform can also be used to stabilize mRNA in lipid-free vaccine formulations. Overall, we stabilized many types of antigens by lyophilization and spray-drying. To date, there are no approved spray-dried vaccines on the market, though several are in development or are in clinical trials. Here we demonstrated that not only are spray-dried vaccines typically thermally stable, but formulation in glassy microparticles enables development of controlled-release formulations for vaccines and therapies.
Author: Coleman, Holly Jane
Language: English
Subfield: Food Science
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7112711760