The role of autophagy in MVA vector-induced immune responses

• Applicant: Professor Dr. Ingo Drexler
• Subject Area: Virology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 452147069

Autophagy has been a hot topic for its regulating role between virus and host interactions in the fields of virology and immunology. For the efficacy of vaccines against pathogens, both innate and adaptive immunity are important. Innate immune responses mediated by or associated with autophagy have been more intensively researched during recent years. However, less is known about the regulation of adaptive immunity by autophagy, especially in vivo. MVA, as a powerful and safe vaccine vector to deliver target antigens for prophylaxis and immunotherapy against infectious diseases and cancer, is an ideal tool for investigating this topic. Our aim in this project is to investigate how autophagy regulates or impacts immune responses after MVA vaccination in vivo. We will perform vaccination experiments in mice with tissue-specific ATG7-, Ulk1 or FIP200-deficiency affecting distinct subsets of antigen presenting or immune regulatory cells such as dendritic cells or macrophages which will therefore lack autophagy. We aim to determine the initial activation of innate immune responses early after vaccination (hours) and will continue to monitor cellular and humoral responses in the acute and memory phase (days, weeks). In addition, comparative proteomic analyses in FACS-sorted dendritic cell or macrophage populations from above mentioned mice will allow to identify key regulatory or effector proteins which have an autophagy-dependent impact on MVA vaccine-induced immune responses. The protective capacity of the viral vector vaccine will be tested in viral or bacterial challenge models. The results will help to optimize future vaccine design based on viral vectors by targeting autophagy for a better immune protection.

• DFG Programme: Research Grants