Immunogenic and tolerogenic properties of monomethoxypoly(ethylene glycol) conjugated proteins.
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.
Caliceti
P
P
Department of Pharmaceutical Sciences, University of Padova, Italy.
Veronese
F M
FM
Jonak
Z
Z
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D007108:Immune Tolerance / Q000187:drug effects*; D016173:Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000276:immunology; D008288:Malaria / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000494:pharmacology; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D011092:Polyethylene Glycols; D016173:Macrophage Colony-Stimulating Factor