Abstract. The UNC Center for Excellence in SARS-CoV2 Serologic Research uses basic and applied research strategies to improve our understanding of the molecular and cellular mechanisms driving serological and humoral immune responses after SARS-CoV2 infection. Our overall goals are to 1) characterize the immune responses elicited to SARS-CoV2 infection, 2) understand the mechanisms driving the serological, humoral and cellular immune responses, 3) determine modifiers of the serologic memory and 4) determine the serological correlates of disease pathogenesis, and protection against future infection. The program includes three Research Projects led by internationally renowned exerts in coronavirus emergence, pathogenesis and immunity (Project 1: Baric), clinical and translational mucosal and systemic immune correlates of disease (Project 2: Bartelt & Margolis) and host-pathogen interactions driving innate and serological immunity (Project 3: Wallet & Maile). Program-wide support is provided by an Administrative Core A and two Shared Resource Cores B and C. Core A includes a robust infrastructure for programmatic oversight as well as participant recruitment, sample collection, tracking and sharing (Core A: Baric & Wallet). Core B is led by world renowned experts in characterization of human antibodies in protection and pathogenesis of disease (Core B: de Silva & Lakshmanane) and will provide recombinant spike protein antigens from SARS-CoV-2 as well as antigen- specific serological assays required for accomplishing the aims of all three Research Projects. Core C is led by serological experts (Core C: Ippolitto, Georgiou & Lavinder) who have revolutionized techniques to comprehensively analyze the molecular composition of the serological antibody repertoire (IgG and IgA) and the cellular antibody repertoire (i.e. B cell receptor) and thus will delineate these repertoires in and isolate human monoclonal antibodies from SARS-CoV-2+ individuals in cohorts defined in each Research Project. All three Research Projects are integrated, and each require the support of all three Cores. To this end, Project 1 will characterize the breadth and potency of polyclonal neutralizing antibody responses as well as determine the kinetics, magnitude and durability of the type-specific and cross neutralizing responses in both the systemic and mucosal compartments. Project 2 will determine the durability and the breadth of anti-SARS-CoV-2 serum antibodies and memory B-cells generated among convalescent plasma donors as well as determine the effect of convalescent plasma on the innate, adaptive and antibody repertoire in recipients. Project 3 will reveal innate immune signatures as a function of serology across the span of natural disease, as well as identify signatures which promote development of protective vs. pathogenic antibody repertoires, while delineating mechanisms of antibody mediated activation and suppression of innate immune function which drives severe vs. mild disease respectively. The integrated expertise of our Team is necessary and sufficient to address the novel cross-cutting hypotheses put forth which will improve our understanding of SARS-CoV2 serological and humoral immunity.

Project Narrative Our highly integrated Center uses novel technologies and reagents to build a portfolio of critical reagents designed to map, track and potentially treat SARS-CoV2 and related infections in the future, while addressing fundamental questions into the molecular and immunologic mechanisms that regulate serologic responses in the mucosal and systemic compartments after natural infection or medical interventions.