Immunogenicity of An Interferon-β1a Product

Abstract

In order to determine whether Blastoferon®, a biosimilar interferon (IFN)-β1a formulation, shares epitopes with other known IFN-β products, a series of neutralization bioassays were performed with a set of well-characterized anti-IFN-β monoclonal antibodies and human sera (World Health Organization Reference Reagents). The bioassay was the interferon-induced inhibition of virus cytopathic effect on human cells in culture (EMC virus and A-549 cells). Computer-calculated results were reported as Tenfold Reduction Units (TRU)/ml. To further assess Blastoferon® immunogenicity, in vivo production of anti-IFN β antibodies was determined in sera of patients included in the pharmacovigilance plan of Blastoferon® by the level of IFN-β1a binding antibodies (by enzyme immunoassay -EIA) and neutralizing antibodies (in the Wish-VSV system). The highly characterized neutralizing monoclonal antibodies A1 and A5 that bind to specific regions of the IFN-β molecule reacted positively with the three β1a IFNs: Blastoferon®, Rebif®, and the IFN-β WHO Second International Standard 00/572. As expected, the non-neutralizing monoclonal antibodies B4 and B7 did not neutralize any of the IFN-β preparations. The commercially available monoclonal antibody B-02 reacted essentially equally with Rebif® and Blastoferon®. The WHO Reference Reagent human serum anti-IFN-β polyclonal antibody neutralized all the IFN-β products, whereas the WHO Reference Reagent human serum anti-IFN-α polyclonal antibody G037-501-572 appropriately failed to react with any of the IFN-β products. On the basis of in vitro reactivity with known, well-characterized monoclonal and polyclonal antibody preparations, Blastoferon® shares immunological determinants with other human interferon-β products, especially IFN-β1a. In vivo antibodies were detected by EIA in 72.9% of 37 chronically treated multiple sclerosis patients, whereas neutralizing antibodies were found in 8.1% of them. Blastoferon® appears to have immunological characteristics comparable to other IFN-β1a products.