Periodic Reporting for period 4 - FuncMAB (High-throughput single-cell phenotypic analysis of functional antibody repertoires)
Período documentado: 2022-08-01 hasta 2024-01-31
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.
In the next step, the researchers explored the impact of introduced changes in immunization on the antibody repertoire, providing insights into the interplay between the two parameters. These studies were done in a murine model system. Data compilation revealed key factors influencing the immune response to vaccination, such as antigenic dose and adjuvants. This work also provided deeper insights into complement activation processes due to antibody binding onto bacterial surfaces and investigated the influence of various agonists on the quality and quantity of the functional antibody repertoire induced by vaccination.
This understanding led to the establishment of criteria for rational vaccine design, resulting in patent applications and ongoing research on peptide mimetics, therapeutic antibodies, and analysis systems to dampen the impact of viral evolution with vaccination. In terms of dissemination of the results, the project led to several high-quality and impact papers in vaccine-related and interdisciplinary journals, talks at universities and conferences, and engagements with the public surrounding the topic of vaccination. The project is also linked to the creation of a start-up.
Overall, the project generated a variety of new measurement methods that can be applied to various fundamental and clinical problems, enhanced our understanding of antibody functionality, and provided insights for the rational design of vaccines.