Primary supervisor: Dr. R. Zahn, Janssen Vaccines & Prevention B.V. , Leiden, The Netherlands
Title: The determine the influence of immunometabolism pathways in the improvement of mucosal vaccination by adenoviral vectors
Collaborators: Prof. J. Hiscott, Institute Pasteur-Rome, Italy ; Dr. A. Bergthaler, The Research Center for Molecular Medicine (CeMM), Vienna, Austria
Early Stage Researcher, TBA (add once Early Stage Researcher list final)
Janssen Vaccines is utilizing its adenoviral based vaccine platform in a variety of infectious disease vaccine programs at different stages of clinical development. Janssen has in depth knowledge of adenoviral vector construction, formulation and evaluation of these in established animal (viral disease) models and aims to expand its knowledge on Ad vaccine induced immunity. Viral pathogens that invade via the mucosal route like influenza and respiratory syncytia virus (RSV), or genital route like papilloma virus and Herpes simplex virus (HSV) likely are more efficiently protected against by vaccination that provides a strong immune response at the mucosal point of entry next to a systemic response. Traditional intramuscular vaccination with genetic vaccines may not provide this local protection and/or require additional modulation for optimal mucosal protection. Adenoviral (Ad) vector vaccine delivery by other routes than the intramuscular one has been confirmed to be achievable (Çuburu et al. Int J Cancer 2018) but needs to be explored and characterized in detail. Which cells are targeted after vaccination in these tissues and how the immune response is initiated in contrast to intramuscular vaccination and subsequent triggering of innate and metabolic pathways is not known. Such knowledge will help to better utilize Ad vectors for mucosal vaccination to prevent for example RSV or HSV infection. The high-level approach will consist of exploring additional mucosal routes of vaccination with adenoviral vectors in established animal models. The adaptive local and systemic immune response (like induced innate immune response profile, targeted immune cells in the draining lymph node and site of infection, and metabolic pathway induction) as well as the protective capacity of these novel application routes will be compared to the traditional route of administration. Part of the work will be performed in collaboration with the laboratories of Prof. J Hiscott and Dr. A. Bergthaler. Further in vitro characterization of Ad induced innate and metabolism pathways will be performed to confirm in vivo findings. To optimize dosage via mucosal routes vaccine formulations will be developed in close collaboration with the formulation department at Janssen and tested for in vivo potency.