Document text
Principal Investigator: Eliver Ghosn
Organization: EMORY UNIVERSITY
Fiscal Year: 2023
Award: $192,880
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Mounting an effective antibody response against SARS-CoV-2 is key to fight off the infection. However,
not all antibodies produced against the virus are protective. Recent studies show that high titers of
immunoglobulin G (IgG) against the SARS-CoV-2 Spike (S) protein during natural infection correlate with disease
severity. The S protein, highlighted due to its receptor-binding role in host cell infection, represents only one of
potentially 29 proteins that are encoded by the SARS-CoV-2 virus. In fact, recent studies show that SARS-CoV-
2 non-structural proteins, including ORF3b, ORF8, ORF9b, and ORF9c, have the ability to suppress host antiviral
type-I interferon (IFN) and elicit sustained antibody responses. These findings raise the question of whether
antibodies produced against these immunomodulatory viral proteins early during the infection could provide
protection against severe COVID-19.
In addition to the antibody specificity to different SARS-CoV-2 proteins, the antibody isotype and
subclass can also influence the disease outcome. However, much of the serology data from SARS-CoV-2-
infected patients mainly focus on IgG and IgM responses to S and nucleocapsid proteins only. In this proposal,
we aim to tackle this problem by developing a new technology that will allow for simultaneous measurement of
8 antibody isotypes and subclasses (IgM, IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgE) against 24 SARS-CoV-2
and endemic HCoV-encoded proteins, including against proteins from emerging virus variants, all in a single
multiplexed assay (Aim 1). We will apply this technology, namely flowBEAT (flow cytometry-based BEads
assay to detect Antigen-specific antibody isoTypes), to 600 serum samples collected from a longitudinal study
(6 timepoints; ≥ 6 months) of a well-characterized cohort of 100 COVID-19 patients presenting with either mild
or severe symptoms (Aim 2). We hypothesize that mild, but not severe, COVID-19 patients will show an early
and sustained antibody subclass against immunomodulatory viral proteins, particularly against viral proteins
known to suppress IFN responses.
We expect this study to provide an in-depth view of the breadth (type, specificity, and longevity) of
antibody responses mounted against 24 SARS-CoV-2- and HCoV-encoded proteins that are associated with
efficient recovery from COVID-19. Our study can also inform on ongoing and future vaccine development by
identifying proteins that generate long-lasting and protective antibody subclasses in the recovered patients.
Finally, the flexible modular feature of flowBEAT can quickly be adapted to study the breadth of antibody
responses in virtually any disease.
Terms: <19S Gamma Globulin><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><7S Gamma Globulin><AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Animal Model><Animal Models and Related Studies><Antibodies><Antibody Response><Antibody Specificity><Antibody titer measurement><Assay><Bioassay><Biologic Assays><Biological Assay><Blood Serum><COVID disease severity><COVID infected patient><COVID patient><COVID positive patient><COVID severity><COVID-19><COVID-19 S protein><COVID-19 associated death><COVID-19 associated fatality><COVID-19 associated mortality><COVID-19 death><COVID-19 disease severity><COVID-19 fatality><COVID-19 induced death><COVID-19 induced fatality><COVID-19 induced mortality><COVID-19 infected patient><COVID-19 mortality><COVID-19 patient><COVID-19 positive patient><COVID-19 related death><COVID-19 related fatality><COVID-19 related mortality><COVID-19 severity><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID19><COVID19 S protein><COVID19 associated death><COVID19 associated fatality><COVID19 associated mortality><COVID19 death><COVID19 disease severity><COVID19 fatality><COVID19 induced death><COVID19 induced fatality><COVID19 induced mortality><COVID19 mortality><COVID19 patient><COVID19 positive patient><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 severity><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 virus><CV-19><CV19><Cell Body><Cells><CoV-2><CoV2><Coronaviridae><Coronavirus><Cross Reactions><Data><Disease><Disease Outcome><Disorder><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Fluorescence><Future><HCoV><HIV><Hospital Admission><Hospitalization><Human><Human Immunodeficiency Viruses><IFN><IgA><IgA1><IgA2><IgE><IgG><IgG1><IgG2><IgG3><IgG4><IgM><Immune response><Immunoglobulin A><Immunoglobulin E><Immunoglobulin G><Immunoglobulin M><Immunological response><Immunomodulation><Individual><Infection><Interferon Type I><Interferons><Investigators><Knowledge><LAV-HTLV-III><Label><Length of Life><Longevity><Longitudinal Studies><Lymphadenopathy-Associated Virus><Measurement><Measures><Methods><Microbeads><Microspheres><Modern Man><Non-structural Protein><Nonstructural Protein><Nucleocapsid Proteins><Pathogenesis><Patients><Prevalence><Proteins><Recovery><Research Personnel><Researchers><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 associated death><SARS-CoV-2 associated fatality><SARS-CoV-2 associated mortality><SARS-CoV-2 death><SARS-CoV-2 disease severity><SARS-CoV-2 fatality><SARS-CoV-2 induced death><SARS-CoV-2 induced fatality><SARS-CoV-2 induced 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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 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Specificity><Symptoms><System><Technology><Variant><Variation><Viral><Viral Gene Products><Viral Gene Proteins><Viral Proteins><Virus><Virus-HIV><Wuhan coronavirus><antibody titering><antigen based detection><antigen detection><cohort><corona virus><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 associated death><coronavirus disease 2019 associated fatality><coronavirus disease 2019 associated mortality><coronavirus disease 2019 death><coronavirus disease 2019 disease severity><coronavirus disease 2019 fatality><coronavirus disease 2019 induced 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coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 mortality><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe acute respiratory syndrome coronavirus 2 related death><severe acute respiratory syndrome coronavirus 2 related fatality><severe acute respiratory syndrome coronavirus 2 related mortality><severe acute respiratory syndrome coronavirus 2 severity><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><social role><vaccine development><virtual><virus protein>