Document text
Principal Investigator: Christopher L King
Organization: CASE WESTERN RESERVE UNIVERSITY
Fiscal Year: 2024
Award: $303,268
Funding agency: National Cancer Institute
Abstract
The duration and nature of humoral immunity to SARS-CoV-2 (CoV2) infection need to be better
understood. While most studies have focused on the immune response in patients with clinical illness,
little is known about the antibody response to CoV2 immediately after exposure and before the onset
of illness, especially in asymptomatic individuals. It is important to understand how this impacts long-
term immunological memory. This supplement aims to extend the objectives of the original grant to
address these gaps in our knowledge by prospectively following household contacts compared to
clinical cases of CoV2 to determine innate and adaptive immune events associated with early viral
exposure. We have conducted a comprehensive evaluation of samples from these patients, including
RNA sequencing of peripheral blood cells, proteomic analysis of oral secretions (the site of initial
CoV2 replication), measurement of viral load using N protein levels, and CoV2-specific IgA and IgG in
blood and saliva. We have identified innate and adaptive signatures associated with viral clearance
and among household contacts that may be associated with their failure to be infected or, if infected,
fail to develop clinical illness. We have identified CoV2 antigens, notably the N protein that is
expressed on CoV-2 infected cells, which are targets of ADCC. Antibodies generated by the N protein
can similarly kill infected cells with various variants of concern, suggesting a potential variant-
transcending target. We have also tracked the humoral immune response in a long-term cohort of
nursing home residents to the CoV-2 mRNA vaccine and subsequent booster responses. This
supplement will continue these ongoing studies and allow their completion.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><7S Gamma Globulin><Address><Antibodies><Antibody Response><Blood><Blood Cells><Blood Reticuloendothelial System><COVID-19 antigen><COVID-19 infection><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><Cell Body><Cells><Clinical><CoV-2><CoV2><Development><Evaluation><Event><Failure><Grant><Household><Humoral Immunities><IgA><IgG><Immune><Immune memory><Immune response><Immunes><Immunity><Immunoglobulin A><Immunoglobulin G><Immunologic Memory><Immunological Memory><Immunological response><Individual><Innate Immune Response><Knowledge><Long-term cohort><Longitudinal cohort><Longterm cohort><Nature><Nursing Homes><Onset of illness><Oral><Patients><Peripheral Blood Cell><Proteins><Proteomics><RNA Seq><RNA sequencing><RNA vaccine><RNA-based vaccine><RNAseq><Research><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 antigen><SARS-CoV-2 infection><SARS-CoV2><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><Saliva><Sampling><Serology test><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 infection><Severe acute respiratory syndrome related corona virus 2><Site><Transcend><Variant><Variation><Viral><Viral load measurement><Wuhan coronavirus><adaptive immune response><anamnestic reaction><antibody-based immunity><coronavirus disease 2019 antigen><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19 virus><developmental><disease onset><disorder onset><hCoV19><host response><immune system response><immunoresponse><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><long term memory><longterm memory><mRNA vaccine><mRNA-based vaccine><nCoV2><nursing home><prospective><response><secondary immune response><serology assay><severe acute respiratory syndrome coronavirus 2 antigen><transcriptome sequencing><transcriptomic sequencing><variants of concern><virus load>