Immunogenicity of aggregates of recombinant human growth hormone in mouse models

J Pharm Sci. 2009 Sep;98(9):3247-64. doi: 10.1002/jps.21834.


Aggregation of recombinant therapeutic protein products is a concern due to their potential to induce immune responses. We examined the immunogenicity of protein aggregates in commercial formulations of recombinant human growth hormone produced by freeze-thawing or agitation, two stresses commonly encountered during manufacturing, shipping and handling of therapeutic protein products. In addition, we subjected each preparation to high-pressure treatment to reduce the size and concentration of aggregates present in the samples. Aggregates existing in a commercial formulation, as well as aggregates induced by freeze-thawing and agitation stresses enhanced immunogenicity in one or more mouse models. The use of high-pressure treatment to reduce size and concentrations of aggregates within recombinant human growth hormone formulations reduced their overall immunogenicity in agreement with the "immunon" hypothesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • Chemical Precipitation
  • Female
  • Freeze Drying
  • Human Growth Hormone / immunology*
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Particle Size
  • Pregnancy
  • Pressure
  • Protein Conformation
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use
  • Solubility


  • Recombinant Proteins
  • Human Growth Hormone