Protein aggregates seem to play a key role among the parameters influencing the antigenicity of interferon alpha (IFN-alpha) in normal and transgenic mice

Pharm Res. 1997 Oct;14(10):1472-8. doi: 10.1023/a:1012193326789.


Purpose: During long-term treatment of various malignant or viral diseases with IFN-alpha up to 20% of patients develop anti-IFN-alpha antibodies for as yet unknown reasons.

Methods: To address this issue, a mouse model using Balb/C mice was established and the relevance of several potentially anti-IFN-alpha antibodies inducing factors was studied.

Results: The model revealed that both a higher frequency of injections and a higher dosage of IFN-alpha were more immunogenic and that the route of administration affected the antibody response to IFN-alpha. The intrinsic immunostimulatory activity of IFN-alpha itself also enhanced the immune response. IFN-alpha protein aggregates (IFN-alpha-IFN-alpha and human serum albumin (HSA)-IFN-alpha aggregates), which were recently identified in all marketed IFN-alpha products, were significantly more immunogenic than IFN-alpha monomers. These aggregates broke the tolerance against human IFN-alpha monomers in human IFN-alpha transgenic mice.

Conclusions: Based on these animal studies it is proposed that the immune response to IFN-alpha in humans is most probably elicited by a combination of several factors among which IFN-alpha protein aggregates seem to play a key role.

Publication types

  • Comparative Study

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibody Formation / immunology
  • Female
  • Humans
  • Injections, Intramuscular
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Interferon Type I / pharmacology
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / chemistry
  • Interferon-alpha / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Poly I-C / pharmacology
  • Recombinant Proteins
  • Serum Albumin / chemistry
  • Serum Albumin / immunology


  • Adjuvants, Immunologic
  • Interferon Type I
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Serum Albumin
  • Poly I-C