Chapman M D, Smith A M, Vailes L D, Arruda L K, Dhanaraj V, Pomés A
Department of Internal Medicine, Asthma and Allergic Diseases Center, University of Virginia, Charlottesville, VA 22908-1355, USA.
J Allergy Clin Immunol. 2000 Sep;106(3):409-18. doi: 10.1067/mai.2000.109832.
Many of the problems associated with using natural allergenic products for allergy diagnosis and treatment can be overcome with use of genetically engineered recombinant allergens. Over the past 10 years, the most important allergens from mites, pollens, animal dander, insects, and foods have been cloned, sequenced, and expressed. In many cases the three-dimensional allergen structure has been determined and B-cell and T-cell epitopes have been mapped. These studies show that allergens have diverse biologic functions (they may be enzymes, enzyme inhibitors, lipocalins, or structural proteins) and that as a rule the allergen function is unrelated to its ability to cause IgE antibody responses. High-level expression systems have been developed to produce recombinant allergens in bacteria, yeast, or insect cells. Recombinant allergens show comparable IgE antibody binding to their natural counterparts (where available) and show excellent reactivity on skin testing and in in vitro diagnostic tests. Cocktails of recombinant allergens can be formulated with predetermined and uniform allergen levels, which could replace natural allergens and result in the development of innovative, patient-based tests for allergy diagnosis. Recombinant allergens also offer the exciting possibility of developing new forms of allergen immunotherapy, including the use of hypoallergens, allergens coupled to IgE suppressive adjuvants, and peptide-based therapies. The production of recombinant allergens as defined molecular entities makes it feasible to consider the possibility of developing prophylactic allergen vaccines. The introduction of recombinant allergens in research and in clinical trials should lead to significant improvements in allergy diagnosis and treatment.
使用基因工程重组变应原可以克服与使用天然变应原产品进行过敏诊断和治疗相关的许多问题。在过去10年中，来自螨虫、花粉、动物皮屑、昆虫和食物的最重要变应原已被克隆、测序和表达。在许多情况下，已确定了变应原的三维结构，并绘制了B细胞和T细胞表位。这些研究表明，变应原有多种生物学功能（它们可能是酶、酶抑制剂、脂质运载蛋白或结构蛋白），而且通常变应原功能与其引发IgE抗体反应的能力无关。已经开发出高水平表达系统，可在细菌、酵母或昆虫细胞中生产重组变应原。重组变应原与天然对应物（如可获得）显示出相当的IgE抗体结合能力，并且在皮肤试验和体外诊断试验中显示出优异的反应性。可以用预先确定的和均匀的变应原水平配制重组变应原混合物，这可以替代天然变应原，并导致开发创新的、基于患者的过敏诊断试验。重组变应原还为开发新形式的变应原免疫疗法提供了令人兴奋的可能性，包括使用低变应原、与IgE抑制佐剂偶联的变应原以及基于肽的疗法。作为确定的分子实体生产重组变应原使得考虑开发预防性变应原疫苗成为可能。在研究和临床试验中引入重组变应原应会显著改善过敏诊断和治疗。
