Ferreira Fátima, Briza Peter, Inführ Daniela, Schmidt Georg, Wallner Michael, Wopfner Nicole, Thalhamer Josef, Achatz Gernot
Department of Molecular Biology, University of Salzburg, A-5020 Salzburg, Austria.
Inflamm Allergy Drug Targets. 2006 Jan;5(1):5-14. doi: 10.2174/187152806775269295.
Molecular cloning and recombinant production of allergens offered new perspectives for the increasing problem of allergies. A variety of preparations are being developed aiming to increase safety and improve efficacy of specific immunotherapy. Recombinant-based approaches are mostly focused on genetic modification of allergens to produce molecules with reduced allergenic activity and conserved antigenicity, i.e. hypoallergens. Studies dealing with genetic modifications of allergen genes reported the production of site-directed mutants, deletion mutants, allergen fragments and oligomers, and allergen chimeras. An alternative to genetic engineering is the chemical modification of pure recombinant allergens. It has been shown that allergens modified with immunostimulatory DNA sequences (allergen-ISS conjugates), which masks IgE epitopes and adds a desirable Th1-inducing character to the allergen molecule. Other chemical modifications include oligomerization by aldehydes (allergoids) and maleylation, which seems to target allergens to particular antigen presenting cells. Several of these modified allergen preparations have been already evaluated for their safety in clinical provocation studies. So far, clinical trials showed the efficacy and safety of immunotherapy with an Amb a 1-ISS conjugate for ragweed pollen-allergic patients. In addition, a preparation consisting of hypoallergenic fragments of Bet v 1 was evaluated for immunotherapy of birch pollen-allergic patients. In parallel, several animal studies have now demonstrated the potential of genetic immunization for allergy treatment in the future.
变应原的分子克隆和重组生产为日益严重的过敏问题提供了新的视角。目前正在研发各种制剂，旨在提高特异性免疫疗法的安全性并改善其疗效。基于重组的方法主要集中在变应原的基因改造上，以产生具有降低的变应原活性和保守抗原性的分子，即低变应原。涉及变应原基因改造的研究报道了定点突变体、缺失突变体、变应原片段和寡聚体以及变应原嵌合体的产生。基因工程的一种替代方法是对纯重组变应原进行化学修饰。已经表明，用免疫刺激DNA序列修饰的变应原（变应原-ISS偶联物）可掩盖IgE表位，并为变应原分子增添所需的诱导Th1的特性。其他化学修饰包括通过醛进行寡聚化（类变应原）和马来酰化，这似乎将变应原靶向特定的抗原呈递细胞。其中几种修饰的变应原制剂已经在临床激发试验中评估了其安全性。到目前为止，临床试验显示了用Amb a 1-ISS偶联物对豚草花粉过敏患者进行免疫疗法的有效性和安全性。此外，还评估了一种由Bet v 1低变应原片段组成的制剂用于桦树花粉过敏患者的免疫疗法。同时，目前一些动物研究已经证明了基因免疫在未来治疗过敏方面的潜力。
