Feasibility of Freeze-Drying Oil-in-Water Emulsion Adjuvants and Subunit Proteins to Enable Single-Vial Vaccine Drug Products
| Autor: | Gaurav Manohar Rajani, Michael P. McCarthy, Steve M. Bishop, Richard L. Remmele, Corinne Cayatte, Bilikallahalli K. Muralidhara, Angie Snell Bennett, Vidyashankara Iyer, Jenny Sun, Sean K. Maynard, Kirsten Schneider-Ohrum, Jason D. Marshall |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Squalene Epstein-Barr Virus Infections Herpesvirus 4 Human medicine.medical_treatment Protein subunit T-Lymphocytes Pharmaceutical Science Monophosphoryl Lipid A 02 engineering and technology Respiratory Syncytial Virus Infections 03 medical and health sciences chemistry.chemical_compound Freeze-drying Antigen Adjuvants Immunologic medicine Animals B-Lymphocytes Immunity Cellular Chromatography Immunogenicity Viral Vaccines 021001 nanoscience & nanotechnology Respiratory Syncytial Viruses Mice Inbred C57BL 030104 developmental biology Freeze Drying chemistry Emulsion Emulsions Female 0210 nano-technology Adjuvant |
| Zdroj: | Journal of pharmaceutical sciences. 106(6) |
| ISSN: | 1520-6017 |
| Popis: | To generate potent vaccine responses, subunit protein antigens typically require coformulation with an adjuvant. Oil-in-water emulsions are among the most widely investigated adjuvants, based on their demonstrated ability to elicit robust antibody and cellular immune responses in the clinic. However, most emulsions cannot be readily frozen or lyophilized, on account of the risk of phase separation, and may have a deleterious effect on protein antigen stability when stored long term as a liquid coformulation. To circumvent this, current emulsion-formulated vaccines generally require a complex multivial presentation with obvious drawbacks, making a single-vial presentation for such products highly desirable. We describe the development of a stable, lyophilized squalene emulsion adjuvant through innovative formulation and process development approaches. On reconstitution, freeze-dried emulsion preparations were found to have a minimal increase in particle size of ∼20 nm and conferred immunogenicity in BALB/c mice similar in potency to freshly prepared emulsion coformulations in liquid form. |
| Databáze: | OpenAIRE |
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