Mahler V, Vrtala S, Kuss O, Diepgen T L, Suck R, Cromwell O, Fiebig H, Hartl A, Thalhamer J, Schuler G, Kraft D, Valenta R
Department of Dermatology, University of Erlangen, Germany.
Clin Exp Allergy. 2004 Jan;34(1):115-22. doi: 10.1111/j.1365-2222.2004.01857.x.
We have recently engineered recombinant derivatives of the major birch pollen allergen Bet v 1 (rBet v 1 fragments and trimer) with strongly reduced allergenic activity.
The aim of this study was the in vivo characterization of potential allergy vaccines based on Al(OH)3-adsorbed genetically modified rBet v 1 derivatives in mice.
BALB/c mice were immunized either with courses of nine injections of increasing doses of Al(OH)3-adsorbed rBet v 1 wild-type, rBet v 1 fragments, rBet v 1 trimer or Al(OH)3 alone in weekly intervals or with three high-dose injections applied in intervals of 3 weeks. Humoral immune responses to rBet v 1 wild-type and homologous plant allergens were measured by ELISA and Western blotting, and the ability of mouse antibodies to inhibit the binding of allergic patients IgE to Bet v 1 was studied by ELISA competition experiments.
In both schemes, hypoallergenic rBet v 1 derivatives induced low IgE but high IgG1 responses against rBet v 1 wild-type. The IgG1 antibodies induced by genetically modified rBet v 1 derivatives cross-reacted with natural Bet v 1 and its homologues from alder (Aln g 1) as well as hazel (Cor a 1) and strongly inhibited the binding of birch pollen allergic patients' IgE to Bet v 1 wild-type.
Genetically modified hypoallergenic rBet v 1 derivatives induce blocking antibodies in vivo. Their safety and efficacy for the treatment of birch pollen and associated plant allergies can now be evaluated in clinical immunotherapy studies.
我们最近构建了主要桦树花粉过敏原Bet v 1的重组衍生物（rBet v 1片段和三聚体），其致敏活性大幅降低。
本研究旨在对基于氢氧化铝吸附的基因改造rBet v 1衍生物的潜在过敏疫苗在小鼠体内进行表征。
用每周一次、共九次递增剂量的氢氧化铝吸附的rBet v 1野生型、rBet v 1片段、rBet v 1三聚体或单独的氢氧化铝对BALB/c小鼠进行免疫接种，或每隔3周进行三次高剂量注射。通过酶联免疫吸附测定法（ELISA）和蛋白质印迹法检测对rBet v 1野生型和同源植物过敏原的体液免疫反应，并通过ELISA竞争实验研究小鼠抗体抑制过敏患者IgE与Bet v 1结合的能力。
在两种方案中，低致敏性rBet v 1衍生物均诱导出针对rBet v 1野生型的低IgE但高IgG1反应。基因改造的rBet v 1衍生物诱导的IgG1抗体与天然Bet v 1及其来自桤木（Aln g 1）以及榛子（Cor a 1）的同源物发生交叉反应，并强烈抑制桦树花粉过敏患者的IgE与Bet v 1野生型的结合。
基因改造的低致敏性rBet v 1衍生物在体内诱导产生阻断抗体。现在可以在临床免疫治疗研究中评估它们治疗桦树花粉及相关植物过敏的安全性和有效性。
