Journal article
An Albumin-Free Formulation for Escherichia coli-Derived Interferon Beta-1b with Decreased Immunogenicity in Immune Tolerant Mice
Journal of interferon & cytokine research, Vol.36(3), pp.192-203
03/01/2016
DOI: 10.1089/jir.2015.0110
PMID: 26824268
Abstract
Human serum albumin (HSA)-free formulation of Escherichia coli-derived human interferon beta (IFN beta-1b) with a high percentage of monomeric protein and low immunogenicity is developed and characterized in the current study.
UV spectroscopy, fluorescence spectroscopy, dynamic light scattering, sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, Micro-Flow Imaging, resonant mass measurement, size exclusion, and reversed-phase high performance liquid chromatographies were applied to assess the effect of excipients on the stability of IFN beta-1b to establish a HSA-free formulation. The antiviral activity of IFN beta-1b was evaluated using human lung carcinoma cell line. Immune tolerant mice to hIFN beta were used to assess the immunogenicity of the HSA-free formulated IFN beta-1b in comparison to Betaferon((R)) drug product and Avonex((R)) drug substance as standards through IgG titering of plasma. HSA-free formulated IFN beta-1b, including 200 mM L-arginine, 200 mM trehalose, and 0.1% n-dodecyl beta-D-maltoside in 10 mM sodium acetate buffer, pH 7.4, showed the highest biological activity. The stability of IFN beta-1b in the HSA-free formulation was monitored for 3 weeks at 4 degrees C and 37 degrees C with relative humidity of 10% and 75%, respectively. Protein aggregation and immunogenicity in transgenic mice were decreased in the HSA-free formulated IFN beta-1b compared to Betaferon. The stability, biological activity, and immunogenicity of the HSA-free formulation and Betaferon were evaluated. Incubation of formulations at 4 degrees C and 37 degrees C for 3 weeks showed that the HSA-free formulated IFN beta-1b was more stable and less immunogenic in transgenic FVB/N mice. Low immunogenicity and the absence of HSA, which reduces the potential risk of viral infection (eg, HIV and HCV), are promising for clinical studies.
Details
- Title: Subtitle
- An Albumin-Free Formulation for Escherichia coli-Derived Interferon Beta-1b with Decreased Immunogenicity in Immune Tolerant Mice
- Creators
- Mohadeseh Haji Abdolvahab - Utrecht UniversityAhmad Fazeli - Department of Research & Development, Zistdaru Danesh Company, Tehran, Iran.Mazda Radmalekshahi - Univ Utrecht, Dept Pharmaceut, UIPS, Univ Weg 99, Utrecht, NetherlandsM. Reza Nejadnik - Centre for Human Drug ResearchMohammad Reza Fazeli - Tehran University of Medical SciencesHuub Schellekens - Utrecht University
- Resource Type
- Journal article
- Publication Details
- Journal of interferon & cytokine research, Vol.36(3), pp.192-203
- Publisher
- Mary Ann Liebert, Inc
- DOI
- 10.1089/jir.2015.0110
- PMID
- 26824268
- ISSN
- 1079-9907
- eISSN
- 1557-7465
- Number of pages
- 12
- Grant note
- Ministry of Science, Research and Technology of Iran
- Language
- English
- Date published
- 03/01/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984420940102771
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