Department of Pharmacology, ALK-Abelló A/S, Hoersholm, Denmark.
Clin Exp Allergy. 2012 Sep;42(9):1356-68. doi: 10.1111/j.1365-2222.2012.04026.x.
Subcutaneous specific immunotherapy (SCIT) has proven sustained clinical efficacy against allergy. The recommended regimen for SCIT is a gradual updosing over a period of weeks. Commonly, in commercial products for SCIT, the specific allergen is formulated with an adjuvant, most often in the form of aluminium hydroxide (AlOH). It has been shown that allergen-specific IgG antibodies are induced as a result of successful SIT.
To investigate the possibility of optimizing the formulation of AlOH-based grass-pollen allergy vaccines for SCIT in a way that allows for shorter updosing regimens while maintaining the immunogenicity of the vaccine.
Mice were immunized with various concentrations of Phleum pratense (Phl p) allergen extract and AlOH or a fixed dilution of the maintenance doses of one conventional and one alternatively formulated vaccine. The kinetics of Phl p-specific IgG antibody responses in serum and spleen T cell responses were determined. Allergenicity, measured as the ability of the formulations to activate human basophils, was also determined. In addition, human T cell responses and the expression of dendritic cell surface markers after vaccine challenge in vitro were analysed.
Specific IgG antibody responses were shown to depend on the AlOH concentration, but not on the allergen concentrations. The immunogenicity of the conventional formulation and the alternative formulation was shown to be similar with regard to the in vivo-induced IgG and T cell responses. In contrast, the allergenicity of the alternative formulation was significantly reduced compared with the conventional formulation.
The optimization of the formulation allows for administration of a lower dose of allergen while maintaining the immunogenicity of the product and at the same time reducing allergenicity.
This study indicates that the optimization of the allergen and the adjuvant formulation could benefit the safety/efficacy profile and allow for shorter updosing.
皮下特异性免疫疗法（SCIT）已被证明对过敏具有持续的临床疗效。SCIT 的推荐方案是在数周内逐渐增加剂量。通常，在用于 SCIT 的商业产品中，特定过敏原与佐剂（最常见的形式为氢氧化铝（AlOH））一起配制。研究表明，成功的 SIT 会诱导过敏原特异性 IgG 抗体。
研究优化基于 AlOH 的草花粉过敏疫苗配方的可能性，使 updosing 方案更短，同时保持疫苗的免疫原性。
用不同浓度的豚草过敏原提取物和 AlOH 或一种常规疫苗和一种替代配方疫苗的维持剂量的固定稀释液对小鼠进行免疫。测定血清和脾脏 T 细胞中 Phleum pratense（Phl p）特异性 IgG 抗体反应的动力学。还测定了配方的变应原性，即配方激活人嗜碱性粒细胞的能力。此外，还分析了体外疫苗挑战后人类 T 细胞反应和树突状细胞表面标志物的表达。
特异性 IgG 抗体反应取决于 AlOH 浓度，但与过敏原浓度无关。与常规配方相比，替代配方的免疫原性在体内诱导的 IgG 和 T 细胞反应方面相似。相比之下，替代配方的变应原性明显低于常规配方。
该配方的优化允许给予较低剂量的过敏原，同时保持产品的免疫原性，同时降低变应原性。
本研究表明，过敏原和佐剂配方的优化可能会改善安全性/疗效，并允许更短的 updosing。
