Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486137 | Journal of Pharmaceutical Sciences | 2011 | 18 Pages |
Abstract
The filoviruses, Ebola virus and Marburg virus, cause severe hemorrhagic fever with up to 90% human mortality. Virusâlike particles of EBOV (eVLPs) and MARV (mVLPs) are attractive vaccine candidates. For the development of stable vaccines, the conformational stability of these two enveloped VLPs produced in insect cells was characterized by various spectroscopic techniques over a wide pH and temperature range. Temperatureâinduced aggregation of the VLPs at various pH values was monitored by light scattering. Temperature/pH empirical phase diagrams (EPDs) of the two VLPs were constructed to summarize the large volume of data generated. The EPDs show that both VLPs lose their conformational integrity above about 50°C-60°C, depending on solution pH. The VLPs were maximally thermal stable in solution at pH 7-8, with a significant reduction in stability at pH 5 and 6. They were much less stable in solution at pH 3-4 due to increased susceptibility of the VLPs to aggregation. The characterization data and conformational stability profiles from these studies provide a basis for selection of optimized solution conditions for further vaccine formulation and longâterm stability studies of eVLPs and mVLPs.
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Lei Hu, Jared M. Trefethen, Yuhong Zeng, Luisa Yee, Satoshi Ohtake, David LechugaâBallesteros, Kelly L. Warfield, M. Javad Aman, Sergey Shulenin, Robert Unfer, Sven G. Enterlein, Vu TruongâLe, David B. Volkin, Sangeeta B. Joshi, C. Russell Middaugh,