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

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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.