| dc.description.abstract | Traditional therapeutics and vaccine regimens have been responsible for saving millions of lives and eliminating some of the deadliest diseases; however, many threats remain, and new threats continue to emerge. Pathogens such as HIV-1 and multi-drug resistant bacteria have become incredibly successful at evading the immune system and have remained resistant to current preventive measures and treatment options. In addition, with the rise of biologic drugs being used to treat disease, new problems such as anti-drug formation have become an issue faced by the healthcare system. This dissertation contains my research efforts on the development and application of novel high-throughput B cell and antibody characterization techniques towards the rational design of next-generation antibody therapeutics and vaccine immunogens in the context of HIV-1 infection, Clostridioides difficile (C. difficile) infection, and inflammatory conditions. In chapter 2, I present LIBRA-seq with epitope mapping, a high-throughput antibody sequencing technology that allows B cell epitope determination to be turned into a sequenceable event. LIBRA-seq with epitope mapping cuts down on the cost, time, and labor of antibody discovery efforts through epitope specificity information being generated earlier in the process. In chapter 3, I investigate the role of the intestinal microbiome in the anti-HIV-1 antibody response. I find that HIV-1 antibodies cross-react with commensal bacterial antigens and that the commensal antigen, EF-Tu can directly alter the anti-HIV antibody response. Lastly, I present two novel approaches to profile the antibody repertoire in two diverse disease settings, C. difficile infection and anti-drug antibody formation. Overall, my work will contribute broadly to the fields of antibody discovery and vaccine design. | |
