Vaccines have had a tremendously positive effect on individual and global health for decades. However, the understanding of their mechanism of action and induced immunological responses is still limited. The concept of vaccine-mediated protection and the quantitation thereof remain especially elusive. Indeed, protection is empirically assayed during clinical trials, and levels and thresholds are defined over time. Here, current testing methods for protection do not provide temporal, spatial, or analytical resolution to expose fundamental differences in the underlying mechanisms that ultimately mediate protection, and therefore the gained understanding is limited. Indeed, immune responses are highly dynamic, heterogeneous and their successful completion involves and needs many different interactions, cells, and functions throughout the organism. Individual cells are the functional units within any immune response, and their varying frequencies and degrees of activity shape and define the response. Therefore, cells from the immune system, their state, activation and ultimately functionality display high dynamic heterogeneity, and there is hence a need for quantitative high-throughput systems that allow for a dynamic, functional single-cell phenotyping, linking function to the individual cells.
Therefore, within this project, we aim to measure, understand, and exploit antibody-mediated vaccine-induced protection on the individual cell and antibody level. By doing so, we aim to not only measure and describe the functional antibody repertoires with single-cell resolution, but also to understand the influences that are introduced by varying vaccination strategies and measure the impact on the quality, quantity, and functionality of the humoral immune response. The overarching objective of this proposal is to quantitatively map antibody functions on the single-cell level, and to use these data sets to understand the selection mechanisms involved in their generation, evolution, and transfer to memory; and to finally exploit the measurement to screen for therapeutic candidates and to accelerate vaccine development.
