The proposed project aims to investigate the polyclonal humoral immune response to a model viral antigen in human samples from pre-exposed individuals. This research integrates advanced techniques, including antigen-specific B-cell sorting, B-cell receptor (BCR) sequencing, and LC-MS/MS-based identification of circulating antigen-specific antibodies. The goal is to link B-cell clonotypes to serum immunoglobulins and resolve functional proteoforms through an immunoproteogenomics approach. The project will involve developing de novo sequencing workflows for antigen-specific antibodies, building proteogenomic pipelines to assemble VH/VL sequences and identify clonotypes. Data will be integrated matching BCR repertoires of PBMCs, tonsil tissue, and matched sera from GSK human biological samples. Computational modeling and machine learning will be essential for antibody identification, epitope prioritization, and cross-cohort comparisons.
The projec...