Antigen-spezifischer "Break of tolerance" in neonatalen Impfungen und konditionierte Boosterung

新生儿的免疫系统暴露在大量的新蛋白质（抗原）中，这些蛋白质大多是无害的。在生命的这个阶段，免疫系统对无害抗原没有反应是至关重要的，这被称为耐受性。耐受性一方面具有保护作用，另一方面可防止产生保护性疫苗接种反应。该项目的目的是以抗原特异性的方式打破这种耐受性，而不干扰新生儿对无害抗原的耐受性。因此，我们将通过重点研究吞噬细胞（抗原呈递细胞）和调节性T细胞（Treg）之间的串扰来研究新生儿接种卡介苗-谷氏芽孢杆菌（结核疫苗）的免疫应答。Treg是免疫反应的普遍抑制剂，保护我们免受有害的免疫反应，如哮喘、过敏或自身免疫等疾病。为了产生保护性免疫反应，必须多次接种疫苗。为了减少疫苗接种数量和提高新生儿疫苗接种反应，我们将采用经典条件反射的新策略。因此，我们将特定风味剂的施用与疫苗的应用相结合（学习阶段）。在下一步，我们将只管理风味，从而提高疫苗接种反应。经典条件反射在免疫系统中起作用，已经在免疫抑制和刺激方法中得到证实。总之，本项目旨在研究Treg在新生儿疫苗接种反应中的功能作用，并阐明创新的疫苗接种策略。

The immune system of neonates is exposed to a tremendous flood of new proteins (antigens) which are mostly harmless. In this phase of life it is from vital importance that the immune system does not respond to nonhazardous antigens and this is called tolerance. Tolerance on the one hand is protective and on the other hand prevents the induction of protective vaccination responses. The aim of this project is to break this tolerance in an antigen specific manner without disturbing neonatal tolerance against nonhazardous antigens. Therefore, we will investigate the immune response against Bacillus Calmette-Guérin vaccination (tuberculosis vaccination) in neonates by focusing on the crosstalk between phagocytes (antigen presenting cells) and regulatory T cells (Treg). Treg are universal inhibitors of immune responses which protect us from detrimental immune responses as in diseases like asthma, allergies or autoimmunity. For the development of a protective immune response vaccines have to be administered multiple times. In order to reduce the number of vaccinations and to improve the neonatal vaccination response we will apply a new strategy by taken advantage of classical conditioning. Therefore, we will condition the administration of a specific flavor to the application of a vaccine (learning phase). In the next step we will only administer the flavor and thereby boost the vaccination response. That classical conditioning is working in the immune system has been shown in immuno suppressive as well as stimulatory approaches. In conclusion, this project aims to investigate the functional role of Treg in neonatal vaccination responses and will elucidate innovative vaccination strategies.