Core C: Immunoglobulin Proteomics in COVID-19

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

↗ Live URL (may be dead)

Document text

Principal Investigator: GREGORY C IPPOLITO
Organization: UNIV OF NORTH CAROLINA CHAPEL HILL
Fiscal Year: 2024
Award: $136,800
Funding agency: National Cancer Institute

Abstract
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.

Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><7S Gamma Globulin><Abate><Advisory Committees><Affinity Chromatography><Antibodies><Antibody Repertoire><Antibody Response><Antigenic Determinants><Area><Assay><B blood cells><B cell><B cell repertoire><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Binding Determinants><Bioassay><Biological Assay><Blood Serum><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 S protein><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 spike><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 virus><COVID-19 years><COVID19 virus><CV-19><Categories><Cessation of life><Circulation><Clinical Treatment Moab><Clinical Trials><Clonality><Cloning><CoV-2><CoV2><Computerized Medical Record><Coronaviridae><Coronavirus><Coronavirus Infectious Disease 2019><County><Data><Data Set><Death><Disease><Disease Outbreaks><Disorder><ELISA><Electronic Medical Record><Enzyme-Linked Immunosorbent Assay><Epitope Mapping><Epitopes><Future><Half-Life><Home><Hu-mABs><Human><IRB><IRBs><IgA><IgG><Immune><Immune Globulins><Immunes><Immunoglobulin A><Immunoglobulin G><Immunoglobulins><Individual><Infection><Institutional Review Boards><Kinetics><Letters><MERS corona virus><MERS coronavirus><MERS virus><MERS-CoV><Masks><Methodology><Middle East Respiratory Syndrome Corona Virus><Middle East Respiratory Syndrome Coronavirus><Middle East Respiratory Syndrome Virus><Middle East Respiratory Syndrome-CoV><Middle East Respiratory Virus><Middle East Respiratory coronavirus><Middle Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome-CoV><Modern Man><Molecular><Molecular Interaction><Monitor><Monoclonal Antibodies><Mucosa><Mucosal Tissue><Mucous Membrane><Natural History><Nature><North Carolina><Outbreaks><Outcomes Research><Patients><Pattern><Persons><Phase><Policies><Population><Prevalence><Proteins><Proteomics><Protocol><Protocols documentation><Research><Research Specimen><Resolution><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 S><SARS-CoV-2 S protein><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 spike><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV2><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Scourge><Serology><Serum><Severe Acute Respiratory Coronavirus><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome related corona virus 2><Source><Specificity><Specimen><Study Subject><Survivors><Swelling><Symptoms><Task Forces><Techniques><Testing><Texas><Time><Transfusion><Translating><US State><Viral><Virus><Work><Wuhan coronavirus><advisory team><affinity purification><cohort><comparative><convalescent plasma><corona virus><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 virus><coronavirus infectious disease-19><cross reactivity><enzyme linked immunoassay><experiment><experimental research><experimental study><experiments><hCoV19><homes><humAbs><human mAbs><human monoclonal antibodies><human monoclonals><in vivo><mAbs><monoclonal Abs><mouse model><murine model><nCoV2><neutralizing antibody><neutralizing mAb><neutralizing monoclonal antibodies><resolutions><response><sample collection><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome-CoV><social><social role><specimen collection><spike proteins on SARS-CoV-2><virtual><zoonotic CoV><zoonotic coronavirus>