The Application of Empirical Phase Diagrams to the Biophysical Characterization and Stabilization of Viral Vaccine Candidates

Abstract

This dissertation describes the application of a composite biophysical approach to the characterization and stabilization of viruses and virus-like particles for vaccine purposes. Spectroscopic, calorimetric, and light-scattering techniques were applied to detect physical changes in multiple aspects of viral architecture following the application of pharmaceutically relevant stress factors. The signals from a variety of these techniques were then combined in a vector-based approach to generate empirical phase diagrams that visually depict changes in each system's physical state as a function of experimental stress factors. These diagrams were then used to determine optimal solution storage conditions and also conditions for screening excipient libraries for appropriate stabilizers.