Single cell features of SARS-CoV-2-specific T cell responses to COVID-19 vaccines in the general (Dutch) population

The COVID-19 pandemic has brought unprecedented understanding of the development, frequency, quality, and kinetics of antigen-specific CD4+ and CD8+ T cells in both the context of natural infection, as well as vaccination. Here we aim to further our understanding of 1) the broader population/vaccination context that gives rise to (sub)optimal T cell responses following COVID-19 vaccination, as well as 2) to identify SARS-CoV-2-specific T cell properties/characteristics at a single cell level that might contribute to differences in vaccine responsiveness. This PhD project will thus thoroughly examine the quality and function of SARS-CoV-2-specific CD4+ and CD8+ T cells, using single-cell techniques such as high-dimensional flow cytometry, single-cell RNA sequencing, and single-cell ATAC sequencing (chromatin accessibility). The Corona Vaccination Trials ongoing at the RIVM provide a unique opportunity to investigate the SARS-CoV-2 specific T cell response in various vaccination settings and groups of interest of the general population. Using these samples, we will identify if and how the COVID-19 vaccination-induced T cell response is influenced by, for instance, the vaccination strategy (e.g., vaccine platform; homologous or heterologous booster vaccination), age, or immune status of the vaccinees (among others). Integration of the data from the various single-cell analyses of SARS-CoV-2-specific T cell responses will be used to define multidimensional profiles of optimal and suboptimal responses induced by various vaccines and vaccination schemes in various age groups. Thus, unravelling the immunological contexts that give rise to (sub)optimal vaccine-induced T cell responses could one day help guide vaccine design or inform public policy.

Contact 
Yvonne Dogariu