Investigating the induction, location and maturation of skin-resident memory T cells in human immunity after yellow fever vaccination strategies.
Abstract
Our skin acts as a crucial immunological barrier, hosting a complex network of immune cells including tissue-resident memory T (TRM) cells. Extensive in vivo data from mouse models suggest that skin TRM cells can provide significant protection against pathogenic (re-)infection with infectious agents, especially those using the skin as entry portal such as skin-to-skin infections, bite infections, or through arthropods like sandflies, mosquitoes or ticks. To date, however, TRM cell induction in the human skin after vaccination remains largely unexplored. Using yellow fever vaccination strategies in humans as a model, my PhD fellowship aims to bridge this gap in fundamental knowledge through (i) validating the impact of the inoculation route and vaccine type on the induction of skin TRM cells, and (ii) performing an in-depth and spatially-resolved characterization at single cell resolution of the human skin TRM response and its maturation environment after vaccination. As such, my thesis will provide novel insights into human skin immunity and tissue-targeted immunization, and inform the design of vaccines tailored to enhance skin-resident immunity against arthropod-borne diseases and other pathogens exploiting dermal entry routes.Researcher(s)
- Promoter: Berens-Riha Nicole
- Fellow: Wouters Janne
Research team(s)
Project type(s)
- Research Project
The road towards memory T cell skin imprinting as a novel correlate of protection against skin infections.
Abstract
Our skin acts as a crucial immunological barrier, hosting a complex network of immune cells including tissue-resident memory T (TRM) cells. Extensive in vivo data from mouse models suggest that skin TRM cells play a pivotal role in local immune surveillance and can provide significant protection against pathogenic (re-)infection with infectious agents. Therefore, establishing a robust population of protective TRM cells in the skin through vaccination holds promise to improve efficacy against infections using the skin as an entry portal, such as skin-to-skin infections, bite infections, or through arthropods like sandflies, mosquitoes or ticks. To date, however, the differentiation, maintenance and protective function of TRM cells in human skin remains largely unexplored. Using rabies vaccination in humans as a model, my PhD fellowship aims to (i) standardize the isolation of antigen-specific TRM cells for clinical implementation, (ii) identify the optimal vaccination route for their induction, and (iii) broadly phenotype the incited TRM cell in human skin. With a standardized assay and low-invasive biomarkers of skin imprinting, we hope to facilitate its uptake in future trials to validate its role as a novel correlate of protection against infections with the skin as a primary entry point.Researcher(s)
- Promoter: Berens-Riha Nicole
- Fellow: Wouters Janne
Research team(s)
Project type(s)
- Research Project