Project description
Antibody analysis for improved vaccines
Our immune system produces a vast number of unique antibodies, each capable of recognising and binding to specific antigens. The process involves the genetic shuffling of specific gene segments to create diverse antibody sequences that can be determined using next-generation sequencing and bioinformatics analysis. Funded by the European Research Council, the Antibodyomics project will employ such a high-throughput antibody repertoire analysis approach to investigate antibody responses after vaccination. Researchers will delve into different vaccination parameters and their role in antibody production. Antibodyomics’ results will advance understanding of the mechanisms of vaccine-mediated antibody responses, paving the way to better vaccines and diagnostics.
Objective
Vaccines and immunodiagnostics have been vital for public health and medicine, however a quantitative molecular understanding of vaccine-induced antibody responses is lacking. Antibody research is currently going through a big-data driven revolution, largely due to progress in next-generation sequencing (NGS) and bioinformatic analysis of antibody repertoires. A main advantage of high-throughput antibody repertoire analysis is that it provides a wealth of quantitative information not possible with other classical methods of antibody analysis (i.e. serum titers); this information includes: clonal distribution and diversity, somatic hypermutation patterns, and lineage tracing. In preliminary work my group has established standardized methods for antibody repertoire NGS, including an experimental-bioinformatic pipeline for error and bias correction that enables highly accurate repertoire sequencing and analysis. The overall goal of this proposal will be to apply high-throughput antibody repertoire analysis for quantitative vaccine profiling and discovery of next-generation immunodiagnostics. Using mouse subunit vaccination as our model system, we will answer for the first time, a fundamental biological question within the context of antibody responses - what is the link between genotype (antibody repertoire) and phenotype (serum antibodies)? We will expand upon this approach for improved rational vaccine design by quantitatively determining the impact of a comprehensive set of subunit vaccination parameters on complete antibody landscapes. Finally, we will develop advanced bioinformatic methods to discover immunodiagnostics based on antibody repertoire sequences. In summary, this proposal lays the foundation for fundamentally new approaches in the quantitative analysis of antibody responses, which long-term will promote the development of next-generation vaccines and immunodiagnostics.
Fields of science
- medical and health scienceshealth sciencespublic health
- medical and health sciencesbasic medicineimmunologyimmunisation
- social sciencespolitical sciencespolitical transitionsrevolutions
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- natural sciencescomputer and information sciencesartificial intelligencemachine learningdeep learning
Programme(s)
Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
8092 Zuerich
Switzerland