Kurzfassung

Viruses are recognized by the imunne system via pattern recognition receptors, 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 of APC, and are thus important for stimulating both...Viruses are recognized by the imunne system via pattern recognition receptors, 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.
Other than most bacterial infections, many viral infections do not result in pathogen clearance but in viral persistence and the development of a chronic infection (e.g. HIV, HepB, HepC, HSV, CMV, HPV). In general, the development of chronic disease is associated with impaired antigen presentation, eiter due to the virus itself or to the chronic inflammatory process. For most of these diseases, an effective therapeutic vaccine is not available. Current vaccines consist either of attenuated virus, which often fails to provide adaquate TLR-mediated DC activation signals, or of a mixture of antigen and „adjuvant“ (i.e. TLR-stimulus), which may differ in biodistribution and tissue half-life, resulting in potential dissociation of the DC activation signal and the antigen itself. Thus, the development of chronic viral infection as well as insufficient vaccination efficacy may be due to inadequate antigen presentation and suboptimal activation of APC.
In this project we will develop an improved antiviral vaccine that is based on targeted, nanoparticle-based delivery of a viral antigen together with optimal activation signals for APC, with the aim of selective uptake, activation and subsequent presentation of the viral antigen by those APC that are optimally capable of inducing effective antiviral immunity.
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