IMMUNOGENICITY OF AN INTERFERON- beta 1a PRODUCT

• Published in: International journal of immunopathology and pharmacology 2011-06, Vol.24 (2), p.499-504
• Main Authors: Kauffman, MA, Sterin-Prync, A, Papouchado, M, Gonzalez, E, Vidal, A J, Grossberg, SE, Chuppa, S, Odoriz, B, Vrech, C, Diez, R A, Ferro, H H
• Format: Article
• Language: English
• ISSN: 0394-6320
• DOI: 10.1177/039463201102400223

In order to determine whether Blastoferon registered , a biosimilar interferon (IFN)- beta 1a formulation, shares epitopes with other known IFN- beta products, a series of neutralization bioassays were performed with a set of well-characterized anti-IFN- beta 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 registered immunogenicity, in vivo production of anti-IFN ss antibodies was determined in sera of patients included in the pharmacovigilance plan of Blastoferon registered by the level of IFN-ss1a 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- beta molecule reacted positively with the three beta 1a IFNs: Blastoferon registered , Rebif registered , and the IFN- beta WHO Second International Standard 00/572. As expected, the non-neutralizing monoclonal antibodies B4 and B7 did not neutralize any of the IFN- beta preparations. The commercially available monoclonal antibody B-02 reacted essentially equally with Rebif registered and Blastoferon registered . The WHO Reference Reagent human serum anti-IFN- beta polyclonal antibody neutralized all the IFN- beta products, whereas the WHO Reference Reagent human serum anti-IFN- alpha polyclonal antibody G037-501-572 appropriately failed to react with any of the IFN- beta products. On the basis of in vitro reactivity with known, well-characterized monoclonal and polyclonal antibody preparations, Blastoferon registered shares immunological determinants with other human interferon- beta products, especially IFN- beta 1a. 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 registered appears to have immunological characteristics comparable to other IFN- beta 1a products.