H1N1 influenza virus-like particles: Physical degradation pathways and identification of stabilizers
✍ Scribed by Julian Kissmann; Sangeeta B. Joshi; Joel R. Haynes; Leslie Dokken; Charles Richardson; C. Russell Middaugh
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 548 KB
- Volume
- 100
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
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.