Characterization and Stability of Trypanosoma cruzi 24-C4 (Tc24-C4), a Candidate Antigen for a Therapeutic Vaccine Against Chagas Disease
| Autor: | Peter J. Hotez, Maria Elena Bottazzi, Amadeo B. Biter, Wen-Hsiang Chen, Jeroen Pollet, Elissa M. Hudspeth, Christopher A. Seid, Sarah Weltje, C. Patrick McAtee, Ulrich Strych |
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| Rok vydání: | 2018 |
| Předmět: |
Protozoan Vaccines
Chagas disease Antigenicity Trypanosoma cruzi 030231 tropical medicine Protozoan Proteins Pharmaceutical Science Antigens Protozoan medicine.disease_cause law.invention 03 medical and health sciences 0302 clinical medicine Antigen law Freezing medicine Humans Chagas Disease 030212 general & internal medicine Escherichia coli biology Protein Stability Immunogenicity Calcium-Binding Proteins Temperature biology.organism_classification medicine.disease Virology Recombinant Proteins Recombinant DNA Cysteine |
| Zdroj: | Journal of Pharmaceutical Sciences. 107:1468-1473 |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2017.12.014 |
| Popis: | Chagas disease due to chronic infection with Trypanosoma cruzi is a neglected cause of heart disease, affecting approximately 6-10 million individuals in Latin America and elsewhere. T. cruzi Tc24, a calcium-binding protein in the flagellar pocket of the parasite, is a candidate antigen for an injectable therapeutic vaccine as an alternative or a complement to chemotherapy. Previously, we reported that a genetically engineered construct from which all cysteine residues had been eliminated (Tc24-C4) yields a recombinant protein with reduced aggregation and improved analytical purity in comparison to the wild-type form, without compromising antigenicity and immunogenicity. We now report that the established process for producing Escherichia coli –expressed Tc24-C4 protein is robust and reproducibly yields protein lots with consistent analytical characteristics, freeze-thaw, accelerated, and long-term stability profiles. The data indicate that, like most proteins, Tc24-C4 should be stable at −80°C, but also at 4°C and room temperature for at least 30 days, and up to 7-15 days at 37°C. Thus, the production process for recombinant Tc24-C4 is suitable for Current Good Manufacturing Practice production and clinical testing, based on process robustness, analytical characteristics, and stability profile. |
| Databáze: | OpenAIRE |
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