Immunogenic and tolerogenic properties of monomethoxypoly(ethylene glycol) conjugated proteins

Farmaco. 1999 Jul 30;54(7):430-7. doi: 10.1016/s0014-827x(99)00048-8.

Abstract

An immunogenic and tolerogenic characterisation of monomethoxypoly(ethylene glycol) conjugated proteins was carried out using, as immunogen models, an anti-malaria chimera monoclonal antibody (PfChMab) and a macrophage colony stimulating factor (M-CSF). Two conjugates of PfChMab were prepared by polymer derivatisation of 19 and 33% protein amino groups and one conjugate of M-CSF was obtained by modification of 24% amino groups. In mice M-CSF was found to elicit rapidly high IgG and IgM levels whereas the monomethoxypoly(ethylene glycol) derivatised M-CSF stimulated a significantly lower immunoresponse. Native PfChMab was found to induce a delayed immunoresponse with high IgM levels but low production of IgG. Furthermore, similar immunogenic profiles were obtained with the native and modified protein forms. The pre-administration of polymer conjugated M-CSF to mice subsequently treated with the native protein was found to suppress up to 75% of anti-native M-CSF IgG, while IgM production was not affected. On the other hand the pre-administration of monomethoxypoly(ethylene glycol) derivatised PfChMab was found to reduce significantly the generation of anti-native PfChMab IgM. Such suppression depended on the degree of modification: the conjugate with the higher number of polymer chains was more effective in suppressing the immunoresponse.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibody Formation / drug effects
  • Colony-Stimulating Factors / chemistry
  • Enzyme-Linked Immunosorbent Assay
  • Immune Tolerance / drug effects*
  • Macrophage Colony-Stimulating Factor / chemistry
  • Macrophage Colony-Stimulating Factor / immunology
  • Malaria / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Weight
  • Polyethylene Glycols / chemical synthesis*
  • Polyethylene Glycols / pharmacology
  • Recombinant Proteins
  • Vaccines, Synthetic / chemistry
  • Vaccines, Synthetic / pharmacology*

Substances

  • Antibodies, Monoclonal
  • Colony-Stimulating Factors
  • Recombinant Proteins
  • Vaccines, Synthetic
  • Polyethylene Glycols
  • Macrophage Colony-Stimulating Factor