Analysing biodistribution of nanoparticulate carriers by imaging tools to optimize their design regarding immune responses after nasal administration – ImaVac

Mucosal vaccination, especially nasal administration, constitutes a strategic approach because i) induced immune responses can be both mucosal and systemic, ii) active ingredients are not exposed to extreme gastrointestinal pH or digestive enzymes, iii) numerous microvilli in the nasal epithelium provide a significant absorption surface, iv) no needles or syringes are required. However, despite the growing interest in these strategies, vaccine imaging remains a major challenge. Yet, it would significantly enhance their effectiveness by improving the understanding of the relationship between their localization and the immune response. Indeed, by using nanoparticles as vaccine carriers and optimizing their synthesis, it becomes possible to direct their localization. The goal of this project is to address this issue by using several nanoformulations based on polylactic acid (PLA) nanoparticles with different physicochemical properties through lipid or polymeric coronas. The encapsulation of contrast agents within these nanoparticles will provide access to various imaging modalities. It will then be possible to track these nanoformulations both within the organism and at the tissue and cellular levels to identify their interactions with various components of the immune system. To demonstrate this concept in the context of nasal administration, the choice of the vaccine formulation is focused on the influenza model, and the nanoparticles will be functionalized with the HA and NA antigens. By correlating their location in lymphoid organs after nasal administration with the quality of immune responses, this project will contribute to elucidating the essential parameters required for the design of nanovaccines.