Recombinant Modified Vaccina Virus Ankara (MVA) and Heat-killed Listeria (HKL) as novel vaccines for the prevention of allergies

儿童对食物和吸入性过敏原过敏的频率随着时间的推移而增加。此外，儿童过敏的特点通常是临床症状按时间顺序排列；食物过敏后出现鼻炎和哮喘(“特应性进行曲”)。目前还没有针对过敏原的预防性治疗或疫苗。尽管研究表明，在儿童早期接触细菌或病毒感染可能会降低患过敏的风险，但其免疫学基础仍存在争议。本项目的假设是重组改良痘苗病毒安卡拉(MVA)和单核细胞增生性李斯特菌鞭毛蛋白与变应原的重组融合蛋白可能是预防食物过敏的有效新型疫苗。花生中的Arah2和卵清蛋白(OVA)被选为模型过敏原，因为Arah2是一种来自最敏感食物之一的非常有效的主要过敏原，而OVA已被用作实验过敏原。疫苗接种和致敏方案将在小鼠的症状评分、IgE抗体产生的调节、细胞免疫反应和Th2细胞因子方面进行评估。此外，还将研究接种食物过敏疫苗对对无关吸入性过敏原的初级致敏作用的影响。拟议的小鼠临床前研究将提供关于这些基于MVA和HKL的新型疫苗预防人类(食物)过敏的潜力的信息。

The frequency of allergies in children to food and inhalant allergens has increased over time. Moreover, allergy in children is often characterized by a chronological sequence of clinical symptoms; onset of rhinitis and asthma following food allergy (“atopic march”). No allergen-specific prophylactic treatments or vaccines are currently available. Although studies suggest that exposure to bacteria or viral infections during early childhood may reduce the risk for the development of allergies, its immunological basis is still controversially discussed. The hypothesis of this project is that recombinant modified vaccinia viruses Ankara (MVA) and recombinant fusion proteins of Listeria monocytogenes flagellin with allergens may be effective novel vaccines for prevention of food allergy. Ara h 2 from peanut and ovalbumin (OVA) are selected as model allergens since Ara h 2 represents a very potent major allergen from one of the most allergenic foods, and OVA has been used as experimental allergen in numerous studies. Vaccination and sensitization protocols will be evaluated in mice in regard to symptom score, modulation of IgE antibody production, cellular immune response, and Th2 cytokines. Furthermore, the effects of vaccination against food allergy on the susceptibility to a primary sensitization to unrelated inhalant allergens will be studied. The proposed pre-clinical studies in mice will give information regarding the potential of these novel MVA and HKL-based vaccines to prevent (food) allergies in humans.