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，儿童过敏通常以临床症状的时间顺序为特征；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方法或疫苗。尽管研究表明，儿童早期接触细菌或病毒感染可能会降低过敏发生的风险，但其免疫学基础仍有争议。本项目假设重组修饰安卡拉痘苗病毒（MVA）和单核增生李斯特菌鞭毛蛋白与过敏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Ara h2和卵清蛋白（OVA）被选择作为模型过敏原，因为Ara h2是来自最易致敏食物之一的一种非常有效的主要过敏原，而OVA在许多研究中被用作实验性过敏原。疫苗接种和致敏方案将在小鼠中评估症状评分、IgE抗体产生的调节、细胞免疫反应和Th2细胞因子。此外，将研究预防食物过敏疫苗对不相关吸入性过敏原致敏的易感性的影响。拟议的小鼠临床前研究将提供有关这些新型MVA和hkl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.