FOR 5898:  AdBHealth: Raising Knowledge & Boosting Technology - Advancing Adenovirus Biology for a Healthy Future

• Subject Area: Medicine ; Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 548065690

Human adenoviruses (HAdV) comprise more than 110 types grouped into species A–G, alongside over 200 non-human AdV. These highly diverse pathogens cause a broad spectrum of diseases and have recently gained growing clinical and technological attention. In particular, immunocompromised patients are at high risk of severe or even fatal HAdV infections. Despite their medical importance, many pathogenic HAdV types remain poorly characterized, primarily due to the lack of suitable infection models for the increasing number of newly identified AdV variants. This situation creates a fundamental paradox: while HAdV are underrecognized and incompletely understood pathogens, certain AdV types represent the most widely used vectors in gene therapy, vaccine development, and oncolytic treatment. Their exceptional amenability to genetic modification and efficiency in gene delivery have enabled major biomedical advances. However, these same properties can also result in unforeseen adverse effects, such as prothrombotic immune reactions observed in some vector-based vaccines. There is, therefore, an urgent need to better understand the AdV biology and to develop specific antiviral strategies, which are currently unavailable. Access to the natural diversity of AdV offers unique opportunities to elucidate determinants of organ and tissue tropism, replication mechanisms, and virus–host interactions. These insights will be essential for designing next-generation AdV vectors that combine improved safety with high efficacy. We hypothesize that a comprehensive understanding of AdV as infectious agents constitutes the foundation for the rational and safe development of advanced vectors and for innovative therapeutic applications. To address this challenge, we propose the establishment of an interdisciplinary DFG RU that will bring together national experts in molecular virology, immunology, cell biology, and translational medicine. We will investigate molecular characteristics, replication strategies, and immune responses to wild-type and vector-derived AdV, including T-cell and antibody reactions, as well as interactions with blood components. These studies will provide essential knowledge of viral recombination, integration potential, and immune modulation processes. State-of-the-art genetic and biochemical methods, complemented by advanced 3D organoid culture systems, will be employed to bridge cellular and tissue-level analyses and to perform preclinical testing. The consortium’s joint expertise will enable the identification of novel host determinants, clarification of immune-related safety issues, and mechanistic insight into vector-associated adverse events. AdBHealth will open new perspectives on AdV diversity, improve the safety and precision of vector applications, and advance therapeutic strategies against severe AdV infections, particularly in immunocompromised patients.

• DFG Programme: Research Units
• International Connection: France

Projects

• AdenoFolds: A Structural Systems Virology Approach to Decode the Adenovirus Interactome (Applicant Bosse, Jens Bernhard )
• Antigen Presentation and T Cell Activation in Adenovirus Oncolytic Therapy and Vaccination (Applicant Engeland, Christine )
• Comparative analysis of human adenovirus immune evasion (Applicants Halenius, Anne ;  Ruzsics, Zsolt )
• Coordination Funds (Applicant Schreiner, Sabrina )
• Dissecting the fate of Human Adenoviruses (HAdV) in blood and endothelial cells (Applicant Ehrhardt, Ph.D., Anja )
• Generation of standardized virus preparations, primary cell culture models from lungs, nasal epithelium, tonsils, and blood including organoids and precision-cut tissue slices (Applicants Aydin, Malik ;  Ehrhardt, Ph.D., Anja )
• In depth characterization of naturally occurring and adoptively transferred HAdV-specific T-cells, their ligands and receptors: perspectives for optimizing protective T-cell immunity against HAdV in transplant recipients (Applicants Eiz-Vesper, Britta ;  Maecker-Kolhoff, Britta )
• Interactions of HAdV with nasal and tonsil tissues: The role of ILCs and NK cells in virus-host immunity and implications for mucosal vaccine development (Applicants Aydin, Malik ;  Ehrhardt, Ph.D., Anja )
• Isolating human neutralizing antibodies targeting adenovirus receptor binding domains (Applicant Krey, Thomas )
• Long-term effects of abortive HAdV infection and DNA persistence in cell culture (Applicants Dobner, Thomas ;  Ip, Wing Hang )
• Project P04: AdV interaction with PF4 and platelets (Applicants Schönborn, Linda ;  Thiele, Thomas )
• Project P07: Influence of HAdV on activation and proliferation capacity of immunogen-specific CD4+ and CD8+ T cells (Applicant Bayer, Wibke )
• Understanding genotype impact on post entry sorting of adenoviral capsids (Applicants Grünewald, Kay ;  Wodrich, Harald )
• Understanding the type-specific role of novel virus-SUMO interplay during AdV infection to orchestrate immunoproteasomes and IFN response (Applicant Schreiner, Sabrina )

• Spokesperson: Professorin Dr. Sabrina Schreiner