Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485577 | Journal of Pharmaceutical Sciences | 2011 | 12 Pages |
Abstract
A simple and rapid approach to vaccine stabilization has been applied to a novel virus-like particle (VLP) that contains the primary influenza antigens (hemagglutinin and neuraminidase surface proteins). A complement of spectroscopic and light scattering techniques was used to characterize the physical stability of influenza VLPs as a function of temperature and pH, two pharmaceutically relevant stress factors. The resulting data set was mathematically converted into a three-color empirical phase diagram (EPD) that illustrates changes in physical state as a function of these stress factors. Conditions of temperature and pH corresponding to apparent phase boundaries in the EPD were then used to screen for inhibitors of VLP aggregation from a library of generally recognized as safe compounds. Several potent inhibitors of VLP aggregation were identified; of these, trehalose, sorbitol, and glycine were all found to exert significant stabilizing effects on viral protein tertiary structure and/or membrane integrity.
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Julian Kissmann, Sangeeta B. Joshi, Joel R. Haynes, Leslie Dokken, Charles Richardson, C. Russell Middaugh,