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Project P07: Influence of HAdV on activation and proliferation capacity of immunogen-specific CD4+ and CD8+ T cells

Subject Area Virology
Term since 2026
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 548065690
 
The aim of the proposed project is an in-depth analysis of the immunogenicity of a broad range of human adenovirus (HAdV) types for the identification of HAdV types with an immunogenicity profile favorable for the development of novel vaccine vectors. For future vaccine development, it is crucial to gain a thorough understanding of the effect of HAdV on antigen-presenting cells and on T cells, and of the underlying mechanisms. Previous studies have shown that the immunogenicity of HAdV types differs vastly, and so-called rare HAdV types with low seroprevalence often exhibit low efficacy when used as vaccine vectors. In this project we will perform an in-depth analysis of the effect of HAdV on dendritic cells derived from human peripheral blood mononuclear cells, comprising the effect on the expression of activating or inhibitory surface molecules and the expression and secretion of effector molecules such as cytokines, chemokines, and type I interferon subtypes. In co-culture models, we will analyze the stimulation of HAdV-specific T cells as well as the effect on T cells that are specific for influenza virus antigens as surrogate vaccine target antigens. Analyzing HAdV with modifications of distinct features in our immunogenicity testing pipeline will allow for elucidating the contribution of different HAdV components and host factors to the overall immunogenicity outcome. To prepare for a future application of novel vaccine vectors, the project aims to test the most promising HAdV types in advanced culture models that include cells such as nasal epithelial cells or platelets in the dendritic cell-T cell co-cultures and advance them into testing as vectors in nasal epithelial cell organoids. Overall, we expect that the proposed project will advance the knowledge about HAdV immunogenicity and the understanding of the immune control of natural infections, and make a valuable contribution to future vaccine development.
DFG Programme Research Units
 
 

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