Wie S I, Wie C W, Lee W Y, Filion L G, Sehon A H, Akerblom E
Int Arch Allergy Appl Immunol. 1981;64(1):84-99.
Our previous findings that antigens, such as ovalbumin (OA) and the extract of ragweed pollen (RAG), could be rendered nonantigenic, nonallergenic and tolerogenic by conjugation with polyethylene glycol (PEG) have been extended in the present study to the synthesis of conjugates of a variety of antigens with monofunctional monomethoxy-PEGs (mPEGS) of different molecular weights by the use of the mixed anhydride method. Thus, mPEGs with molecular weights of 2,000, 5,000, 10,000 and 20,000 were coupled to proteins such as dog serum albumin (DA), bovine pancreatic ribonuclease, OA and the constituents of pollen, helminth and bacterial allergens (RAG, Timothy grass pollen, Ascaris suum and Micropolyspora faeni). All these mPEG conjugates depressed markedly the ongoing IgE antibody formation in sensitized animals, in spite of additional injections of the sensitizing dose of the appropriate antigen. Moreover, the allergenicity of the proteins was either totally abolished or markedly reduced after coupling to mPEGs. Conjugates of DA and OA of varying degree of substitution (i.e. number of mPEG molecules attached per protein molecule) were prepared with mPEGs of different molecular weights and their immunological properties were assessed. It appears that, for a series of tolerogenic conjugates of the same antigen, there exists some inverse relationship between the degree of substitution and the molecular weight of mPEG, i.e. a high level of tolerogenicity with a concomitant reduction or total loss of allergenicity was achieved with a lower degree of substitution utilizing mPEGs of increasing molecular weights. On the basis of these results, it is concluded that a variety of allergens may be converted by conjugation with mPEGs to tolerogenic products with a potential for use in the therapy of patients allergic to a wide spectrum of common allergens.
我们之前的研究发现，诸如卵清蛋白（OA）和豚草花粉提取物（RAG）等抗原，通过与聚乙二醇（PEG）结合可变得无抗原性、无致敏性且具有耐受性。在本研究中，这一发现通过混合酸酐法扩展到了多种抗原与不同分子量的单功能单甲氧基-PEG（mPEG）的缀合物合成。因此，分子量为2000、5000、10000和20000的mPEG与犬血清白蛋白（DA）、牛胰核糖核酸酶、OA以及花粉、蠕虫和细菌过敏原（RAG、梯牧草花粉、猪蛔虫和嗜热放线菌）的成分等蛋白质进行了偶联。尽管再次注射了适当抗原的致敏剂量，但所有这些mPEG缀合物均显著抑制了致敏动物中正在进行的IgE抗体形成。此外，蛋白质与mPEG偶联后，其致敏性要么完全消除，要么显著降低。用不同分子量的mPEG制备了不同取代度（即每个蛋白质分子连接的mPEG分子数）的DA和OA缀合物，并评估了它们的免疫学特性。似乎对于同一抗原的一系列耐受性缀合物，取代度与mPEG分子量之间存在某种反比关系，即利用分子量增加的mPEG，较低的取代度可实现高耐受性水平，同时伴随着致敏性的降低或完全丧失。基于这些结果，可以得出结论，多种过敏原通过与mPEG结合可转化为耐受性产物，有可能用于治疗对多种常见过敏原过敏的患者。
