Immunogenicity of an interferon-beta1a product

Int J Immunopathol Pharmacol. Apr-Jun 2011;24(2):499-504. doi: 10.1177/039463201102400223.

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.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing / blood
  • Cell Line, Tumor
  • Cytopathogenic Effect, Viral / drug effects
  • Encephalomyocarditis virus / drug effects
  • Encephalomyocarditis virus / pathogenicity
  • Enzyme-Linked Immunosorbent Assay
  • Epitope Mapping
  • Epitopes*
  • Humans
  • Interferon beta-1a
  • Interferon beta-1b
  • Interferon-beta / immunology*
  • Interferon-beta / therapeutic use
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology
  • Neutralization Tests

Substances

  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • Interferon beta-1b
  • Interferon-beta
  • Interferon beta-1a