title: Immunogenicity of an interferon-beta1a product.
abstract: In order to determine whether Blastoferon®, 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® immunogenicity, in vivo production of anti-IFN beta antibodies was determined in sera of patients included in the pharmacovigilance plan of Blastoferon® by the level of IFN- beta 1a 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®, Rebif®, 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® and Blastoferon®. 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® 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® appears to have immunological characteristics comparable to other IFN- beta 1a products.
authors.forename: M A
authors.initials: MA
authors.lastname: Kauffman
authors.forename: A
authors.initials: A
authors.lastname: Sterin-Prync
authors.forename: M
authors.initials: M
authors.lastname: Papouchado
authors.forename: E
authors.initials: E
authors.lastname: González
authors.forename: A J
authors.initials: AJ
authors.lastname: Vidal
authors.forename: S E
authors.initials: SE
authors.lastname: Grossberg
authors.forename: S
authors.initials: S
authors.lastname: Chuppa
authors.forename: B
authors.initials: B
authors.lastname: Odoriz
authors.forename: C
authors.initials: C
authors.lastname: Vrech
authors.forename: R A
authors.initials: RA
authors.lastname: Diez
authors.forename: H H
authors.initials: HH
authors.lastname: Ferro
mesh_terms: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing / Q000097:blood; D045744:Cell Line, Tumor; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004686:Encephalomyocarditis virus / Q000187:drug effects / Q000472:pathogenicity; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D009500:Neutralization Tests
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a