Biophysical characterization and immunization studies of dominant negative inhibitor (DNI), a candidate anthrax toxin subunit vaccine
| Autor: | C. Russell Middaugh, Chrystal M. Chadwick, Lei Hu, Vidyashankara Iyer, Nishant Kumar Jain, Kiran K. Andra, David B. Volkin, Robert N. Brey, Nicholas J. Mantis, Sangeeta B. Joshi, James G. Bann, Carole E. Schanté, David J. Vance |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Protein Conformation
medicine.medical_treatment Anthrax toxin Protein subunit Bacterial Toxins Immunology Aluminum Hydroxide Anthrax Vaccines Biology Biophysical Phenomena law.invention Microbiology Anthrax Adjuvants Immunologic Drug Stability law medicine Animals Immunology and Allergy Pharmacology Antigens Bacterial Mice Inbred BALB C Anthrax vaccines Protein Stability Immunogenicity Temperature Biological activity biology.organism_classification Bacillus anthracis Protein Subunits Freeze Drying Vaccines Subunit Recombinant DNA Immunization Adjuvant Research Paper |
| Zdroj: | Human Vaccines & Immunotherapeutics. 9:2362-2370 |
| ISSN: | 2164-554X 2164-5515 |
| Popis: | Dominant Negative Inhibitor (DNI) is a translocation-deficient homolog of recombinant protective antigen of Bacillus anthracis that is a candidate for a next generation anthrax vaccine. This study demonstrates that the biophysical characteristics of the DNI protein stored in lyophilized form at 4°C for 8 y were similar to recombinant Protective Antigen (rPA). To provide information on the accelerated stability of DNI, samples in the lyophilized form were subjected to thermal stress (40°C and 70°C for up to 4 weeks) and thoroughly evaluated using various biophysical and chemical characterization techniques. Results demonstrate preserved structural stability of the DNI protein under extreme conditions, suggesting long-term stability can be achieved for a vaccine that employs DNI, as desired for a biodefense countermeasure. Furthermore, the biological activity of the stressed DNI bound to the adjuvant Alhydrogel (®) was evaluated in mice and it was found that the immunogenicity DNI was not affected by thermal stress. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|