A modified immune tolerant mouse model to study the immunogenicity of recombinant human interferon beta

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 (hIFN beta) (C57Bl/6, and C57Bl/6 x 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 C57B1/6 x 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 C57B1/6 (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 rhIFN beta formulations compared to the C57BI/6, and C57BI/6 x FVB/N transgenic mouse models. The new FVB/N transgenic mouse model was more sensitive for all tested rhIFN beta 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 C57BI/6, and C57B1/6 x FVB/N strains. (C) 2014 Elsevier B.V. All rights reserved.