Stability of a Trivalent Recombinant Protein Vaccine Formulation Against Botulinum Neurotoxin During Storage in Aqueous Solution
| Autor: | Theodore W. Randolph, Julianne Cooper, John F. Carpenter, Tia Estey, Christina Vessely, Ian Henderson, LaToya Jones Braun, Rajiv Nayar |
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| Rok vydání: | 2009 |
| Předmět: |
Botulinum Toxins
Protein Conformation medicine.medical_treatment Pharmaceutical Science Salt (chemistry) Article law.invention chemistry.chemical_compound Adsorption Protein structure Adjuvants Immunologic law medicine Antigens Aluminum Compounds Clostridium chemistry.chemical_classification Aqueous solution Protein Stability Chemistry Phosphate Combinatorial chemistry Recombinant Proteins Bacterial vaccine Biochemistry Bacterial Vaccines Recombinant DNA sense organs Adjuvant Protein Binding |
| Zdroj: | Journal of Pharmaceutical Sciences. 98:2970-2993 |
| ISSN: | 0022-3549 |
| DOI: | 10.1002/jps.21498 |
| Popis: | The adsorption of recombinant botulinum neurotoxin (BoNT) protein-derived vaccine antigens to aluminum salt adjuvants has been previously studied for the development of a trivalent vaccine against the neurotoxins (Vessely et al., in press, J Pharm Sci). The current paper describes an investigation of the stability of recombinant BoNT antigens adsorbed to aluminum salt adjuvants during storage in aqueous solution. Both chemical and physical changes occurred during storage. Phosphate groups in the buffer exchanged with hydroxyl groups on the adjuvant surface. The resulting changes in solution pH and adjuvant surface chemistry promoted more favorable electrostatic interaction between the BoNT proteins and the surface, possibly increasing the affinity of the proteins for the surface during storage. Fluorescence and UV spectroscopy suggested changes to protein structure during storage, whereas differential scanning calorimetry showed changes to thermal processes related to protein conformation and/or surface adsorption. The consequence of the chemical and physical changes to the proteins was a decrease in the ability to desorb protein from the adjuvant surface during storage. Overall, the results of this study emphasize the utility of a thorough characterization of the interactions between protein antigens and aluminum salt adjuvants. |
| Databáze: | OpenAIRE |
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