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Principal Investigator: Ralph S Baric
Organization: UNIV OF NORTH CAROLINA CHAPEL HILL
Fiscal Year: 2024
Award: $820,801
Funding agency: National Cancer Institute
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.
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response><Immunologically><Immunologics><Individual><Infection><Infrastructure><International><Intervention><Intervention Strategies><Kinetics><Maps><Mediating><Medical><Medical center><Memory><Memory B Cell><Memory B-Lymphocyte><Modern Man><Molecular><Mucosa><Mucosal Tissue><Mucous Membrane><North Carolina><Pathogenesis><Pathogenicity><Patient Recruitments><Peptide/Protein Chemistry><Persons><Productivity><Protein Chemistry><Proteins><R-Series Research Projects><R01 Mechanism><R01 Program><Reagent><Recombinants><Reporting><Research><Research Grants><Research Project Grants><Research Projects><Research Resources><Resource Sharing><Resources><Role><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CO-V2><SARS-COVID-2><SARS-CoV><SARS-CoV-1><SARS-CoV-2><SARS-CoV-2 antibody><SARS-CoV-2 antigen><SARS-CoV-2 infection><SARS-CoV-2 therapy><SARS-CoV-2 treatment><SARS-CoV2><SARS-CoV2 infection><SARS-Related Coronavirus><SARS-associated corona 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