Document text
Principal Investigator: GRACE Yoonheekim GOMBOLAY
Organization: EMORY UNIVERSITY
Fiscal Year: 2024
Award: $201,398
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
Mounting an effective antibody and cellular immune response to SARS-CoV-2 vaccination is critical for its
efficacy to reduce the risk of severe complications and death in COVID-19. Patients with multiple sclerosis
(pwMS) are at increased risk for severe COVID-19 and can have altered immune responses to SARS-CoV-2
vaccination. In addition, the type of disease-modifying therapy (DMT) further increases the risk for
breakthrough COVID-19 infection and risk for severe COVID-19 and death in pwMS. For example, while anti-
CD20 monoclonal antibodies (anti-CD20 mAbs) and sphingosine-1-phosphate receptor modulators (S1PMs)
both decrease antibody response to SARS-CoV-2 in adult pwMS, the patient’s SARS-CoV-2-specific T-cell
responses are blunted in S1PMs but not anti-CD20 mAbs. Although much is known about adult pwMS, limited
data is available on vaccine responses in pediatric-onset multiple sclerosis (POMS) on similar therapies.
Vulnerable and understudied, children have different immune systems than adults and can mount different
immune responses to SARS-CoV-2 immunization. Here, we propose investigating how different
immunotherapies (anti-CD20 mAbs vs. S1PM) affect vaccine response in pwMS across age. We will use our
new multiparameter technology, flowBEAT, to measure the type (IgM, IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgE)
and specificity (22 antigens, including structural and non-structural SARS-CoV-2 and HCoV proteins, and a
panel to detect autoantibodies associated with COVID-19 severity) of antibody responses to SARS-CoV-2
vaccination and their ability to neutralize SARS-CoV-2 infection, along with pseudovirus neutralization assays
(Aim 1). We will also characterize the phenotype and function of the patient’s SARS-CoV-2-specific B-cell and
T-cell subsets using Hi-D flow and mass cytometry (Aim 2). Characterizing the SARS-CoV-2-specific humoral
(antibodies) and cellular (memory B and T cell) responses after vaccination will determine whether the different
immunotherapy regimens, anti-CD20 mAbs vs. S1PMs, can affect the development of a protective vaccine
response, including robust neutralizing antibodies in pwMS across age. Our preliminary data suggest deficient
IgG1 responses in POMS on S1PM but not on anti-CD20 mAbs. Thus, we hypothesize that the immunotherapy
type (anti-CD20 mAbs vs. S1PM) will predict the quality of the memory B- and T-cell responses, including
alterations in neutralizing antibodies, and that this protective immune response will depend on age. We expect
this work to inform therapeutic decisions prescribed to vulnerable MS patients and guide future vaccine strategies
to maximize vaccine efficacy in other patients on similar immunotherapies.
Terms: <0-11 years old><19S Gamma Globulin><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><21+ years old><Admission><Admission activity><Adult><Adult Human><Affect><Age><Antibodies><Antibody Response><Antigens><Assay><Autoantibodies><Autoantigens><Autologous Antigens><B blood cells><B cell><B cell depletion therapy><B cell directed therapy><B cell targeted therapy><B cell therapies><B cell therapy><B cells><B-Cells><B-Lymphocytes><B-cell><Bioassay><Biological Assay><Blood Plasma Cell><Bp35><C2B8 Monoclonal Antibody><CD20><COVID complications><COVID disease severity><COVID infected patient><COVID patient><COVID positive patient><COVID related complications><COVID severity><COVID-19 antibody><COVID-19 associated death><COVID-19 associated fatality><COVID-19 associated mortality><COVID-19 complications><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 infection><COVID-19 mortality><COVID-19 patient><COVID-19 positive patient><COVID-19 related complications><COVID-19 related death><COVID-19 related fatality><COVID-19 related mortality><COVID-19 related risk><COVID-19 risk><COVID-19 risk factor><COVID-19 severity><COVID-19 vaccination><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><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 infection><COVID19 mortality><COVID19 patient><COVID19 positive patient><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 severity><COVID19 virus><Cell Mediated Immunology><Cell-Mediated Immunity><Cellular Immunity><Cessation of life><Child><Child Youth><Children (0-21)><CoV-2><CoV2><Coronaviridae><Coronavirus><Cytometry><Data><Death><Development><Dimensions><Disease><Disorder><Disseminated Sclerosis><Edg Receptors><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Future><Germinal Center><HCoV><Hospital Admission><Hospitalization><Human><Humoral Immunities><IgA1><IgA2><IgE><IgG1><IgG2><IgG3><IgG4><IgM><Immune><Immune mediated therapy><Immune response><Immune system><Immunes><Immunization><Immunoglobulin E><Immunoglobulin M><Immunological response><Immunologically Directed Therapy><Immunosuppressants><Immunosuppressive Agents><Immunosuppressive drug><Immunosuppressive treatment><Immunotherapy><Impairment><Infection><Intensive Care Units><Leu-16><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic nodes><MS patient><MS4A1><MS4A1 gene><MS4A2><MabThera><Measures><Memory B Cell><Memory B-Lymphocyte><Messenger RNA><MoAb CD20><Modern Man><Monoclonal Antibody CD20><Multiple Sclerosis><Participant><Pathway interactions><Patients><Phenotype><Plasma Cells><Plasmacytes><Production><Proteins><Regimen><Risk><Risk Reduction><Rituxan><S1P Receptor><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 antibody><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 mortality><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 mortality><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 related death><SARS-CoV-2 related fatality><SARS-CoV-2 related mortality><SARS-CoV-2 severity><SARS-CoV-2 vaccination><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><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><Self-Antigens><Serology><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 coronavirus 2 vaccination><Severe acute respiratory syndrome related corona virus 2><Shapes><Specificity><Sphingosine-1-Phosphate Receptor><Structure of germinal center of lymph node><T cell response><T-Cell Subsets><T-Cells><T-Lymphocyte><T-Lymphocyte Subsets><Technology><Therapeutic><Vaccinated><Vaccination><Vaccines><Vulnerable Populations><Work><Wuhan coronavirus><adaptive immune response><adulthood><age group><ages><anti-CD20><antibody against COVID-19><antibody against SARS-CoV-2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><antibody-based immunity><antigen based detection><antigen detection><autoimmune antibody><autoreactive antibody><cohort><complications due to COVID-19><corona virus><coronavirus disease 2019 antibody><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 death><coronavirus disease 2019 induced fatality><coronavirus disease 2019 induced mortality><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 mortality><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 related death><coronavirus disease 2019 related fatality><coronavirus disease 2019 related mortality><coronavirus disease 2019 risk><coronavirus disease 2019 risk factor><coronavirus disease 2019 severity><coronavirus disease 2019 vaccination><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease severity><coronavirus disease-19 mortality><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus patient><death due to COVID-19><death due to COVID19><death due to SARS-CoV-2><death due to coronavirus disease 2019><death due to severe acute respiratory syndrome coronavirus 2><death in COVID><death in COVID-19><death in SARS-CoV-2><death in coronavirus disease><death in coronavirus disease 2019><death in severe acute respiratory syndrome coronavirus 2><detect antigen><developmental><fatality due to COVID-19><fatality due to COVID19><fatality due to SARS-CoV-2><fatality due to coronavirus disease 2019><fatality due to severe acute respiratory syndrome coronavirus 2><flow cytophotometry><hCoV19><high dimensionality><host response><human CoV><human corona virus><human coronavirus><immune suppressive agent><immune suppressor><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immunization strategy><immuno therapy><immunogen><immunoresponse><immunosuppressive substance><immunosuppressor><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><insular sclerosis><kids><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><lymph gland><lymph nodes><lymphnodes><mRNA><mortality due to COVID-19><mortality due to COVID19><mortality due to SARS-CoV-2><mortality due to coronavirus disease 2019><mortality due to severe acute respiratory syndrome coronavirus 2><multiple sclerosis patient><nCoV2><neutralizing antibody><new technology><novel><novel technologies><pathway><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><patients with MS><patients with multiple sclerosis><pediatric multiple sclerosis><pediatric onset MS><pediatric onset multiple sclerosis><people with Multiple sclerosis><plasmocyte><prevent><preventing><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><response><risk associated with COVID-19><risk factor associated with COVID-19><risk factor related to COVID-19><risk related to COVID-19><risk-reducing><rituximab><self reactive antibody><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 antibody><severe acute respiratory syndrome coronavirus 2 associated death><severe acute respiratory syndrome coronavirus 2 associated fatality><severe acute respiratory syndrome coronavirus 2 associated mortality><severe acute respiratory syndrome coronavirus 2 death><severe acute respiratory syndrome coronavirus 2 disease severity><severe acute respiratory syndrome coronavirus 2 fatality><severe acute respiratory syndrome coronavirus 2 induced death><severe acute respiratory syndrome coronavirus 2 induced fatality><severe acute respiratory syndrome coronavirus 2 induced mortality><severe acute respiratory syndrome 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><systematic review><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><thymus derived lymphocyte><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccination strategy><vaccine effectiveness><vaccine efficacy><vaccine response><vaccine responsiveness><vaccine strategy><vaccine-induced response><variants of concern><vulnerable group><vulnerable individual><vulnerable people><youngster>