Kurzfassung

In the course of natural immune responses, pathogens are recognized by the immune system via pattern recognition receptors (PRRs), which results in activation of innate immunity, as well as by specific antigen (Ag) receptors on T and B cells, generating the adaptive immune response. To activate T and B cells, Ag needs to be presented by Ag-presenting cells (APC), which in turn need to be activated. PRR, especially the group of toll-like-receptors (TLRs), are among the most potent activators...In the course of natural immune responses, pathogens are recognized by the immune system via pattern recognition receptors (PRR´s), which results in activation of innate immunity, as well as by specific antigen (Ag) receptors on T and B cells, generating the adaptive immune response. To activate T and B cells, Ag needs to be presented by Ag-presenting cells (APC), which in turn need to be activated. PRR, especially the group of toll-like-receptors (TLR´s), are among the most potent activators of APC, and are thus important for stimulating both the adaptive and the acquired immune response.
To generate therapeutic immune responses e.g. towards tumors or chronic infectious diseases, currently available vaccine strategies are often clearly sufficient, and attempts to improve the vaccine efficacy by optimizing the adjuvant or the composition of the Ag have mostly failed. As a more promising approach, DC have been generated ex-vivo, activated to become functionally mature, loaded with Ag and injected back into the host. This resulted in some degree of immue activation but generally failed to induce reliable therapeutic immunity.
It is the aim of this project to selectively deliver Ag to DC in situ and at the same time activate them to induce their optimal immunostimulatory acitivity. In this collaborative effort, we shall contribute to the development of an improved vaccine strategy that is based on targeted, nanoparticle-based delivery of a model antigen together with optimal activation signals for APC, with the aim of selective uptake, activation and subsequent presentation of the Ag by those APC that are optimally capable of inducing effective immunity.
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