Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Antibodies play a crucial role in the immune response to infections and the balance of the immune system. Serological diagnostics rely on the detection of antibodies for diagnosis, which labs can utilize in the development of monoclonal antibodies for targeted therapies. Monoclonal antibodies generated in laboratories are used as therapeutics to treat infectious diseases, cancer and autoimmune disorders. However, the development of therapeutic monoclonal antibodies using conventional approaches is a labour-intensive undertaking. Here, I propose using mass spectrometry, immunoaffinity enrichment, multi-dimensional proteomics, and machine learning-empowered data analysis as an innovative platform for the discovery and sequencing of disease-specific antibodies directly from the patients' blood serum. Coupling cutting-edge and first-of-its-kind in Canada mass spectrometry instrumentation with optimized immunoaffinity enrichment methods using viral antigens previously established in lab, will generate substantially more informative data on antibody repertoires and sequences. For the first time, our platform may enable the sequencing and assembly of human antibodies and facilitate the rapid development of monoclonal therapeutic antibodies. The project's focus will be on unveiling the polyclonal antibodies against Respiratory Syncytial Virus (RSV) as a model system and Influenza A, a priority pathogen with pandemic potential, to demonstrate the feasibility of pandemic preparedness implications. Additionally, utilizing multi-dimensional proteomics and mass spectrometry analysis will enable a deeper evaluation of diversity and repertoires of polyclonal antibodies in patient samples. Taken together, cutting-edge mass spectrometry techniques with biochemical antibody enrichment methods will provide a platform for in-depth serology of infectious diseases, uncover novel mechanisms of immune response, and facilitate therapeutic development to aid in pandemic preparedness.