Research Core C will be integral to the examination of serological antibody repertoires in COVID-19 study subjects as well as in convalescent plasmas obtained from survivors. Core C will employ a set of unique experimental techniques including a proteomic methodology (Ig-seq) for the identification of the monoclonal sequences and for determining the epitope specificity and function of the secreted component immunoglobulins (IgG and IgA) comprising the polyclonal response to SARS-CoV-2. The UT Core will examine the persistence of individual serum mAb clonotypes as a function of time and also the relationships between the IgA and IgG repertoires in circulation and in BAL. To date, all human SARS-CoV-2-reactive antibodies have been isolated exclusively from B cells transiently circulating in the periphery. The significance of the abundance, durability, and interconnectivity of serological antibodies?IgG versus IgA, neutralizing versus non-neutralizing, mucosal versus systemic?shall become clear as this research core comprehensively analyzes the molecular composition of anti-viral IgG and IgA and traces the B-cell subpopulations from which they arose. These studies will be enabled by robust sample collections from UNC Chapel Hill and from UT Austin. We expect that the experimental outcomes of Research Core C will clarify (i) the extent of antibody breadth and potency of the constituent IgG and IgA in the serological repertoires and role in protection (via viral blockade or through Fc dependent mechanisms) against endemic and zoonotic coronaviruses in mouse models (Project 1), and (ii) the detailed molecular-level characterization of convalescent plasmas used for transfusion therapy in a COVID-19 clinical trial (Project 2). Comparative analyses shall be performed to determine adaptive immune signatures which may explain differential patterns among asymptomatic, oligosymptomatic, and severe disease. This research will be critical to our understanding the nature and complexity of human antibody responses against the SARS-CoV-2 pandemic scourge.
