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

新生儿的免疫系统暴露在大量新的蛋白质(抗原)中，这些蛋白质(抗原)大多是无害的。在生命的这个阶段，免疫系统对无害的抗原不产生反应是至关重要的，这被称为耐受性。耐受性一方面是保护性的，另一方面也阻止了保护性疫苗接种反应的诱导。该项目的目的是以一种抗原特异性的方式打破这种耐受性，而不会干扰新生儿对无害抗原的耐受性。因此，我们将通过研究吞噬细胞(抗原提呈细胞)和调节性T细胞(Treg)之间的串扰来研究新生儿对卡介苗-盖林疫苗(结核疫苗)的免疫应答。Treg是免疫反应的通用抑制剂，可以保护我们免受哮喘、过敏或自身免疫等疾病的有害免疫反应的影响。为了发展一种保护性免疫反应，疫苗必须多次接种。为了减少接种次数，提高新生儿的免疫应答，我们将利用经典条件反射的优势，采用一种新的策略。因此，我们将在疫苗的应用(学习阶段)中规定特定口味的使用条件。在下一步，我们将只管理味道，从而提高疫苗接种反应。经典的条件反射在免疫系统中起作用，这一点已经在免疫抑制和刺激方法中得到了证明。总之，该项目旨在研究Treg在新生儿接种反应中的功能作用，并将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.