Vaccination has been proven to be extremely efficient against infectious diseases, but we still want to enhance vaccination efficacy. Morning vaccination for Influenza, Tuberculosis and even SARS-CoV-2 has been shown to be more efficient compared to afternoon/evening but the reason for this is still unknown.
Dendritic cells (DCs) play a key role in vaccination by processing antigens and presenting them to T cells in lymph nodes, eliciting protective adaptive immunity. We and others have shown that peripheral DCs have shown a robust circadian or 24 hours rhythms in antigen processing and migration to lymph nodes. The skin represents an optimal target for vaccination because of its large network of skin DCs. This project aims to optimise vaccination by determining the best time of the day for vaccination of skin DCs and the most efficient way to deliver vaccines to these cells. This will be achieved by understanding the clock biology of skin DCs and by developing a microneedle patch in order to deliver the vaccine directly to the skin. DCs display different metabolic states according to their activation status or migratory capacity. The student will investigate the metabolic status of the mice skin at different time and with or without clock proteins. The main technics used will be Seahorse, it allows us to know which metabolic pathway are predominant in the skin by tracking the mitochondrial respiration and glycolysis. The student will also study specifically the metabolism of skin DC by a new technic call Spectral flow cytometry allowing us to have a single cell information. These results on the metabolic status of the skin at different time of the day have never been done before, therefore those results will help us to understand the skin circadian rhythm and find the best time of the day for vaccination.
