There is a need for efficient methods to treat food allergy; however, no immunotherapeutic method has yet been satisfactory due to the high rate of unpredictable severe reactions and the limited efficacy. Therefore, modified versions of food allergens have been suggested as alternatives to the parent proteins for immunotherapy. The aim of the study was to compare the inherent allergenicity of the native and denatured version of the cow's milk proteins β‐lactoglobulin and α‐lactalbumin, and to study the impact of the use of Al(OH)₃ as an adjuvant. Brown Norway rats were immunized intraperitoneally with either native or denatured β‐lactoglobulin or α‐lactalbumin, with or without the use of Al(OH)₃ as adjuvant. Antibody responses were analysed in various ways by means of different ELISAs. Both the immunogenicity and the sensitizing capacity of the cow's milk allergens were influenced by their globular folding, with the native version being more allergenic than the denatured counterpart. The native folded proteins mainly raised antibodies against conformational epitope, whereas the denatured versions predominantly raised antibodies against linear epitopes. Most interestingly, the study showed that the use of Al(OH)₃, besides increasing immunogenicity and sensitizing capacity of the cow's milk allergens, caused a modification of the specificity of the antibodies raised against the native version of the proteins. Adsorption of the native forms of the allergens to Al(OH)₃ caused a significant greater proportion of antibodies raised against linear epitopes, stressing that the adsorption induced a partly unfolding of the proteins. This may have implications for IT safety and efficacy.

中文翻译：

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氢氧化铝作为佐剂可调节特异性抗体反应-布朗挪威的一项针对天然和变性牛奶过敏原的大鼠研究。

需要一种有效的方法来治疗食物过敏；然而，由于不可预测的严重反应的高发生率和有限的疗效，目前尚无令人满意的免疫治疗方法。因此，已经提出了食物变应原的修饰形式作为用于免疫治疗的亲本蛋白质的替代物。这项研究的目的是比较牛乳蛋白β-乳球蛋白和α-乳白蛋白的天然和变性版本的固有致敏性，并研究使用Al（OH）₃作为佐剂的影响。使用天然或变性的β-乳球蛋白或α-乳清蛋白腹膜内免疫棕色挪威大鼠，不论是否使用Al（OH）₃作为佐剂。通过不同的ELISA以各种方式分析抗体应答。牛奶过敏原的免疫原性和致敏能力都受到其球状折叠的影响，其中天然变种比变性变种更易致敏。天然折叠蛋白主要产生针对构象表位的抗体，而变性形式主要产生针对线性表位的抗体。最有趣的是，该研究表明，Al（OH）_3的使用，除了提高牛奶过敏原的免疫原性和敏化能力外，还引起了针对天然蛋白形式的抗体的特异性改变。天然形式的过敏原对Al（OH）_3的吸附引起明显增加的针对线性表位的抗体，强调吸附引起蛋白质的部分展开。这可能会影响IT安全性和有效性。