Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach
| Autor: | Christopher B. Fox, Quinton M. Dowling, Michelle Archer, Dawn M. Fedor, Po-Wei D. Huang, Alicia M. Schwartz, Natasha Dubois Cauwelaert, Thomas S. Vedvick, Elyse A. Beebe, Mark T. Orr, Ryan M. Kramer |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
controlled temperature chain medicine.medical_treatment Chemistry Pharmaceutical Pharmaceutical Science Pharmacology International Journal of Nanomedicine Drug Discovery Tuberculosis Vaccines Original Research Thermostability Immunity Cellular biology Chemistry Immunogenicity Temperature General Medicine Hydrogen-Ion Concentration Lipids Drug product Emulsions Female Adjuvant Tuberculosis lyophilization Biophysics Bioengineering Biomaterials Mycobacterium tuberculosis Excipients 03 medical and health sciences adjuvant Antigen Adjuvants Immunologic Nephelometry and Turbidimetry GRAS medicine Animals Particle Size formulation development Organic Chemistry biology.organism_classification medicine.disease Dynamic Light Scattering Mice Inbred C57BL design of experiments 030104 developmental biology Freeze Drying Antibody Formation Nanoparticles |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | Ryan M Kramer, Michelle C Archer, Mark T Orr, Natasha Dubois Cauwelaert, Elyse A Beebe, Po-wei D Huang, Quinton M Dowling, Alicia M Schwartz, Dawn M Fedor, Thomas S Vedvick, Christopher B Fox Infectious Disease Research Institute, Seattle, WA, USA Background: Adjuvants have the potential to increase the efficacy of protein-based vaccines but need to be maintained within specific temperature and storage conditions. Lyophilization can be used to increase the thermostability of protein pharmaceuticals; however, no marketed vaccine that contains an adjuvant is currently lyophilized, and lyophilization of oil-in-water nanoemulsion adjuvants presents a specific challenge. We have previously demonstrated the feasibility of lyophilizing a candidate adjuvanted protein vaccine against Mycobacterium tuberculosis (Mtb), ID93 + GLA-SE, and the subsequent improvement of thermostability; however, further development is required to prevent physicochemical changes and degradation of the TLR4 agonist glucopyranosyl lipid adjuvant formulated in an oil-in-water nanoemulsion (SE). Materials and methods: In this study, we took a systematic approach to the development of a thermostable product by first identifying compatible solution conditions and stabilizing excipients for both antigen and adjuvant. Next, we applied a design-of-experiments approach to identify stable lyophilized drug product formulations. Results: We identified specific formulations that contain disaccharide or a combination of disaccharide and mannitol that can achieve substantially improved thermostability and maintain immunogenicity in a mouse model when tested in accelerated and real-time stability studies. Conclusion: These efforts will aid in the development of a platform formulation for use with other similar vaccines. Keywords: adjuvant, lyophilization, tuberculosis, formulation development, design of experiments, controlled temperature chain, GRAS |
| Databáze: | OpenAIRE |
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