Host and Viral Determinants of Antibody-Mediated Immunity Following SARS-CoV-2 Infection and Vaccination

Abstract

Human respiratory viral pathogens have led to numerous pandemics over the course of history, each causing significant mortality, morbidity, and economic losses. The emergence of SARS-CoV-2 in late 2019, a human beta-coronavirus, stands as one of the latest examples. A critical component in responding to the spread of SARS-CoV-2 was the development of serological assays to measure antibody responses to both infection and vaccination. This thesis focuses on the comprehensive characterization of antibody-mediated responses to coronaviruses at the population level and in defined cohorts, enabled by a newly developed high-throughput, robust, and flexible serological platform. This approach supported large-scale investigations into the influence of demographics on viral seroepidemiology and vaccine-induced immunity. Our data provided critical insights to guide and monitor public health measures and informed how various antibody responses differ between certain demographic groups. We also investigated how pre-existing immunity to other human coronaviruses can functionally influence antibody responses to SARS-CoV-2. Additionally, we explored the roles of autoantibodies in the context of SARS-CoV-2 infection. Lastly, we investigated viral genomic evolution of highly pathogenic human coronaviruses (SARS-CoV, SARS-CoV-2, and MERS-CoV) and their associated host transcriptomic responses. Collectively, this work advances our understanding of the factors shaping antibody responses to respiratory pathogens and vaccines, highlighting the influence of demographic variables, pre-existing immunity, autoantibodies, and viral genomic evolution.