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Principal Investigator: Scott Dexter Boyd
Organization: STANFORD UNIVERSITY
Fiscal Year: 2024
Award: $187,844
Funding agency: National Cancer Institute
PROJECT 2: SUMMARY
The B cell and plasma cell populations that give rise to serum and mucosal antibodies will ultimately determine
the effectiveness and duration of an individual’s humoral immune response to SARS-CoV-2 infection. We will
use several mutually-supporting strategies to analyze these cells in the Boyd lab: single B cell phenotyping, B
cell receptor (BCR) deep sequencing and determination of antigen specificity with DNA-barcoded antigen
tetramers; bulk B cell immunoglobulin gene repertoire sequencing; and monoclonal antibody production from
antigen-specific B cells. In complementary strategy, the Jardetzky lab will make use of yeast display libraries of
patient-derived single-chain antibody variable fragments (ScFv) enriched for native heavy-light chain pairing to
determine the antigen specificity of hundreds to thousands of antigen-specific clones per patient. In longitudinal
peripheral blood samples and nasal biopsy samples we will thoroughly characterize antigen-specific B cell
clones in patient responses to SARS-CoV-2. We hypothesize that with these data we will be able to determine
which features of B cell clonal responses to SARS-CoV-2 are associated with differences in COVID-19 disease
severity and differences between populations groups stratified by age, sex, ethnicity and pre-existing
conditions, or dysregulated immunity in the context of checkpoint blockade treatment. We further hypothesize
that analysis of memory B cell populations together with serological responses may predict which individuals
will have longer-lasting humoral protection against reexposure to SARS-CoV-2. Finally, we will evaluate the B
cell responses stimulated by natural infection compared to vaccination, beginning with the Covaxx peptide-
based vaccine cohort, but with the expectation that additional vaccines will be approved for use during the
period of this project funding. In addition to studying aspects of the B cell responses that differ among these
clinical scenarios, we will search for features such as “convergent” virus-specific BCRs of highly similar
sequences shared between different individuals that may have prognostic value, for example by revealing that
an individual has a potent neutralizing antibody response to SARS-CoV-2. Our Aims are the following:
Specific Aim 1: Analyze B cell responses in acute COVID-19 disease.
Specific Aim 2: Evaluate the formation of B cell memory to SARS-CoV-2.
Specific Aim 3: Analyze mucosal B cell and plasma cell responses to SARS-CoV-2 compared to responses of
B cells in the blood.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Active Follow-up><Acute><Affinity><Antibodies><Antibody Response><Antibody Specificity><Antibody-Secreting Cells><Antigenic Determinants><Antigens><Assay><B blood cells><B cell><B cell receptor><B cells><B-Cell Activation><B-Cell Antigen Receptor><B-Cell Subsets><B-Cells><B-Lymphocyte Subsets><B-Lymphocytes><B-cell><Bar Codes><Binding Determinants><Bioassay><Biological Assay><Biopsy><Biopsy Sample><Biopsy Specimen><Blood><Blood Plasma Cell><Blood Reticuloendothelial System><Blood Sample><Blood Serum><Blood specimen><CD71><COVID disease severity><COVID severity><COVID-19 disease severity><COVID-19 exposure><COVID-19 immunity><COVID-19 infection><COVID-19 severity><COVID-19 virus><COVID-19 virus infection><COVID19 disease severity><COVID19 infection><COVID19 severity><COVID19 virus><Cell Body><Cell Differentiation><Cell Differentiation process><Cells><Clinical><Clinical Data><Clinical Treatment Moab><Clonal Evolution><Clonal Expansion><Clone Cells><CoV-2><CoV2><Collaborations><Communities><DNA><Data><Data Analyses><Data Analysis><Data Bases><Databases><Deoxyribonucleic Acid><Disease><Disorder><Dissociation><Epitopes><Ethnic Origin><Ethnicity><Frequencies><Funding><Ig Genes><Ig Somatic Hypermutation><Immune response><Immunity><Immunofluorescence Microscopy><Immunoglobulin Genes><Immunoglobulin Somatic Hypermutation><Immunoglobulin-Secreting Cells><Immunologic Receptors><Immunological Receptors><Immunological response><Individual><Infection><Joints><Libraries><Light><Link><Measures><Memory B Cell><Memory B-Lymphocyte><Monoclonal Antibodies><Mucosa><Mucosal Tissue><Mucous Membrane><Mutate><Nasal><Nasal Mucosa><Nasal Passages Nose><Nose><Patients><Phenotype><Photoradiation><Plasma Cells><Plasmablast><Plasmacytes><Population><Population Group><Research Resources><Research Specimen><Resources><Respiratory System, Nose, Nasal Passages><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 disease severity><SARS-CoV-2 exposure><SARS-CoV-2 immunity><SARS-CoV-2 infection><SARS-CoV-2 severity><SARS-CoV2><SARS-CoV2 exposure><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Serology><Serum><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-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 exposure><Severe acute respiratory syndrome coronavirus 2 immunity><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Site><Sorting><Specificity><Specimen><Structure of mucous membrane of nose><T cell response><TFR gene><TFR protein><TFR1><TFRC><TFRC gene><TRFR><Time><Transferrin Receptor><Transferrin Receptor 1><Vaccination><Vaccines><Viral Antigens><Virus><Work><Wuhan coronavirus><Yeasts><activated B cells><active followup><acute COVID-19><acute SARS-CoV-2 infection><acute phase of COVID-19><acute phase of SARS-CoV-2 infection><age stratification><assess effectiveness><barcode><cellular differentiation><check point blockade><checkpoint blockade><cohort><coronavirus disease 2019 disease severity><coronavirus disease 2019 exposure><coronavirus disease 2019 immunity><coronavirus disease 2019 infection><coronavirus disease 2019 severity><coronavirus disease 2019 virus><coronavirus disease severity><coronavirus disease-19 virus><data base><data interpretation><deep sequencing><design><designing><determine effectiveness><effectiveness assessment><effectiveness evaluation><evaluate effectiveness><examine effectiveness><expectation><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><follow up><follow-up><followed up><followup><global gene expression><global transcription profile><hCoV19><host response><immune check point blockade><immune checkpoint blockade><immune receptor><immune system response><immunity against COVID-19><immunity against SARS-CoV-2><immunity against Severe acute respiratory syndrome coronavirus 2><immunity against coronavirus disease 2019><immunity to COVID-19><immunity to SARS-CoV-2><immunity to Severe acute respiratory syndrome coronavirus 2><immunity to coronavirus disease 2019><immunogen><immunoresponse><improved><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><interest><long term memory><longterm memory><mAbs><monoclonal Abs><monoclonal antibody production><nCoV2><neutralizing antibody><patient response><patient specific response><peptide based vaccine><peripheral blood><plasmocyte><prognostic ability><prognostic power><prognostic utility><prognostic value><response><responsive patient><severe acute respiratory syndrome coronavirus 2 disease severity><severe acute respiratory syndrome coronavirus 2 severity><sex><somatic hypermutation><synergism><transcriptome><vaccine response><vaccine responsiveness><vaccine-induced response><virology><virus antigen>