title: A modified immune tolerant mouse model to study the immunogenicity of recombinant human interferon beta.
abstract: Interferon beta may induce antibodies in multiple sclerosis patients and the incidence of immunogenicity depends on the type of product. These antibodies can reduce the efficacy of interferon beta. Two transgenic immune tolerant mouse models for human interferon beta (hIFNβ) (C57Bl/6, and C57Bl/6×FVB/N F1 hybrid mice) have been developed previously for studying immunogenicity. These models, however, may not be used for every interferon beta product because of the lack of immunogenicity in the wildtype genetic background. We therefore developed a modified transgenic mouse model by backcrossing the F1 hybrid C57Bl/6×FVB/N transgenic mice with wildtype FVB/N for 10 generations. These F10 offspring (referred to hear as FVB/N) have a genetic background consisting of mostly FVB/N (99.9%) and very little C57Bl/6 (0.1%), and are expected to have the more sensitive antibody producing phenotype of the parental FVB/N strain. The newly generated "FVB/N" strain was assessed for antibody formation against different rhIFNβ formulations compared to the C57Bl/6, and C57Bl/6×FVB/N transgenic mouse models. The new FVB/N transgenic mouse model was more sensitive for all tested rhIFNβ products, and the difference in antibody titers between the transgenic and non-transgenic mice of the FVB/N strain was much bigger compared to the antibody levels of the C57Bl/6, and C57Bl/6×FVB/N strains.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, The Netherlands. Electronic address: M.HajiAbdolvahab@uu.nl.
authors.forename: Mohadeseh Haji
authors.initials: MH
authors.lastname: Abdolvahab
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, The Netherlands.
authors.forename: Vera
authors.initials: V
authors.lastname: Brinks
authors.affiliation: Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Department of Innovation Studies, Utrecht University, Utrecht, The Netherlands.
authors.forename: Huub
authors.initials: H
authors.lastname: Schellekens
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D016899:Interferon-beta / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology*; D013045:Species Specificity
chemical_list: D000906:Antibodies; D011994:Recombinant Proteins; D016899:Interferon-beta
keywords: Immune tolerance; Immunogenicity; Mouse models; Recombinant human interferon beta