North Carolina Seronet Center for Excellence

Abstract.The UNC Center for Excellence in SARS-CoV2 Serologic Research uses basic and applied researchstrategies to improve our understanding of the molecular and cellular mechanisms driving serological andhumoral immune responses after SARS-CoV2 infection. Our overall goals are to 1) characterize the immuneresponses elicited to SARS-CoV2 infection, 2) understand the mechanisms driving the serological, humoral andcellular immune responses, 3) determine modifiers of the serologic memory and 4) determine the serologicalcorrelates of disease pathogenesis, and protection against future infection. The program includes threeResearch 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 andC. Core A includes a robust infrastructure for programmatic oversight as well as participant recruitment, samplecollection, tracking and sharing (Core A: Baric & Wallet). Core B is led by world renowned experts incharacterization 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 byserological experts (Core C: Ippolitto, Georgiou & Lavinder) who have revolutionized techniques tocomprehensively analyze the molecular composition of the serological antibody repertoire (IgG and IgA) and thecellular antibody repertoire (i.e. B cell receptor) and thus will delineate these repertoires in and isolate humanmonoclonal antibodies from SARS-CoV-2+ individuals in cohorts defined in each Research Project. All threeResearch Projects are integrated, and each require the support of all three Cores. To this end, Project 1 willcharacterize the breadth and potency of polyclonal neutralizing antibody responses as well as determine thekinetics, magnitude and durability of the type-specific and cross neutralizing responses in both the systemic andmucosal compartments. Project 2 will determine the durability and the breadth of anti-SARS-CoV-2 serumantibodies and memory B-cells generated among convalescent plasma donors as well as determine the effectof convalescent plasma on the innate, adaptive and antibody repertoire in recipients. Project 3 will reveal innateimmune signatures as a function of serology across the span of natural disease, as well as identify signatureswhich promote development of protective vs. pathogenic antibody repertoires, while delineating mechanisms ofantibody mediated activation and suppression of innate immune function which drives severe vs. mild diseaserespectively. The integrated expertise of our Team is necessary and sufficient to address the novel cross-cuttinghypotheses put forth which will improve our understanding of SARS-CoV2 serological and humoral immunity.