Gregory James A, Shepley-McTaggart Ariel, Umpierrez Michelle, Hurlburt Barry K, Maleki Soheila J, Sampson Hugh A, Mayfield Stephen P, Berin M Cecilia
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Plant Biotechnol J. 2016 Jul;14(7):1541-50. doi: 10.1111/pbi.12515. Epub 2016 Jan 23.
Peanut allergy is an IgE-mediated adverse reaction to a subset of proteins found in peanuts. Immunotherapy aims to desensitize allergic patients through repeated and escalating exposures for several months to years using extracts or flours. The complex mix of proteins and variability between preparations complicates immunotherapy studies. Moreover, peanut immunotherapy is associated with frequent negative side effects and patients are often at risk of allergic reactions once immunotherapy is discontinued. Allergen-specific approaches using recombinant proteins are an attractive alternative because they allow more precise dosing and the opportunity to engineer proteins with improved safety profiles. We tested whether Ara h 1 and Ara h 2, two major peanut allergens, could be produced using chloroplast of the unicellular eukaryotic alga, Chlamydomonas reinhardtii. C. reinhardtii is novel host for producing allergens that is genetically tractable, inexpensive and easy to grow, and is able to produce more complex proteins than bacterial hosts. Compared to the native proteins, algal-produced Ara h 1 core domain and Ara h 2 have a reduced affinity for IgE from peanut-allergic patients. We further found that immunotherapy using algal-produced Ara h 1 core domain confers protection from peanut-induced anaphylaxis in a murine model of peanut allergy.
花生过敏是一种由免疫球蛋白E(IgE)介导的,对花生中部分蛋白质产生的不良反应。免疫疗法旨在通过使用提取物或花生粉,让过敏患者在数月至数年的时间里反复、逐步增加接触剂量,从而实现脱敏。蛋白质的复杂组合以及制剂之间的差异使得免疫疗法的研究变得复杂。此外,花生免疫疗法常常伴随着负面副作用,而且一旦停止免疫疗法,患者往往有发生过敏反应的风险。使用重组蛋白的过敏原特异性方法是一种有吸引力的替代方案,因为它们能实现更精确的剂量控制,并有机会设计出安全性更高的蛋白质。我们测试了两种主要的花生过敏原——Ara h 1和Ara h 2,是否可以利用单细胞真核藻类莱茵衣藻的叶绿体来生产。莱茵衣藻是一种生产过敏原的新型宿主,它具有遗传易处理、成本低且易于培养的特点,并且能够生产比细菌宿主更复杂的蛋白质。与天然蛋白质相比,藻类生产的Ara h 1核心结构域和Ara h 2与花生过敏患者的IgE的亲和力降低。我们进一步发现,在花生过敏的小鼠模型中,使用藻类生产的Ara h 1核心结构域进行免疫疗法可使小鼠免受花生诱导的过敏反应。