title: Interferon immunogenicity: technical evaluation of interferon-alpha 2a.
abstract: Observations from some studies with interferon-alpha 2a (IFN-alpha 2a) have shown the presence of neutralizing antibodies in a proportion of patients. As a result, an investigation into the production of antibodies to IFN-alpha 2a was undertaken. A number of technical aspects of its production and storage were investigated, including the possibility of an incorrect structure, which could affect the immunogenicity of the IFN-alpha 2a molecule. These investigations demonstrated the presence, in vials of IFN-alpha 2a, of both interferon-interferon (IFN-IFN) aggregates and aggregates of interferon with human serum albumin (HSA), the excipient of the galenical form of IFN-alpha 2a (IFN-HSA) aggregates. The amount of aggregates is temperature dependent, there being very little increase in aggregate content over time when vials are stored at 4 degrees C. The relative immunogenicity of IFN-alpha 2a increased when the vials were stored at ambient temperature but not when stored at 4 degrees C. These findings demonstrate that the immunogenicity of IFN-alpha 2a is likely to be related to the storage temperature. Storage of IFN-alpha 2a vials at 2-8 degrees C is now recommended. A new formulation has been introduced that does not contain HSA as an excipient, removing the possibility of IFN-HSA aggregation.
authors.affiliation: Department of Biotech Production and Process Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hochuli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004926:Escherichia coli; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011309:Preservation, Biological; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins