tetano
Editor, Senior Moderator
J Pharm Sci. 2010 Jul 28. [Epub ahead of print]
H1N1 influenza virus-like particles: Physical degradation pathways and identification of stabilizers.
Kissmann J, Joshi SB, Haynes JR, Dokken L, Richardson C, Middaugh CR.
Department of Pharmaceutical Chemistry, University of Kansas, Multidisciplinary Research Building, 2030 Becker Drive, Lawrence, Kansas 66047.
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. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci XX:1-12, 2010.
PMID: 20669328 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20669328
H1N1 influenza virus-like particles: Physical degradation pathways and identification of stabilizers.
Kissmann J, Joshi SB, Haynes JR, Dokken L, Richardson C, Middaugh CR.
Department of Pharmaceutical Chemistry, University of Kansas, Multidisciplinary Research Building, 2030 Becker Drive, Lawrence, Kansas 66047.
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. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci XX:1-12, 2010.
PMID: 20669328 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20669328