Document text
Principal Investigator: Genevieve Giny Fouda Amou ou
Organization: WEILL MEDICAL COLL OF CORNELL UNIV
Fiscal Year: 2023
Award: $706,463
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract
As of March 2021, SARS-CoV-2 has caused more than 50 million infections and 2 million
deaths, constituting an unprecedented pandemic in the modern world. While infected individuals
rapidly develop IgG responses against the viral Spike after infection, some studies have
indicated that individuals with mild infection generate weaker neutralizing Ab responses
compared to those with severe disease. The durability of the immune response following natural
infection and its afforded protection against subsequent infections and emerging related variants
remain unclear. Interestingly, unlike other respiratory viruses, children are rarely develop severe
disease following SARS CoV-2 infection. Antibody responses in hospitalized children and those
who developed the multisystem inflammatory syndrome (MIS-C) have been characterized, but,
there is a gap in knowledge of the magnitude, quality, durability, and breadth of antibody
responses in asymptomatic or mildly symptomatic children, responses that may contribute to
making children less susceptible to severe infection compared to adults. Moreover, the
possibiltiy of reinfection or infection with a novel variant in previously-infected children is not
known, making the possibility of restarting congregate settings for children without a childhood
vaccine quite challenging. Our overarching goal is to characterize the kinetics, function,
breadth, and durability of humoral immune responses elicited by SARS-CoV-2 infection across
the pediatric age spectrum in comparison to that of adults. We hypothesize that pediatric
immune responses to SARS-CoV-2 infection is distinct from that of adults, and associates with
protection against symptomatic disease and durability of immunity. Using samples from two
unique ongoing community studies of SARS-CoV-2 infections in adults and children, we will test
our hypothesis through the following aims: 1) Define the similarities and differences in the
kinetics, magnitude, specificity, function and durability of SARS-CoV-2-specific Ab responses in
children and adults; 2) Investigate the breadth and potency of antibody responses in SARS-
CoV-2-infected children against established and predicted variants of SARS-CoV-2; and 3)
Define the SARS-CoV-2-specific B cell repertoire and characterize the potency of pediatric
SARS CoV-2-specific monoclonal antibodies. These evaluations will identify immune correlates
of protection against severe disease and provide insights for immunization strategies towards
the long term control of SARS CoV-2 which will likely become an endemic pathogen.
Terms: <0-11 years old><18 year old><18 years of age><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><21+ years old><7S Gamma Globulin><AIDS Virus><Ab-dependent cellular cytotoxicity><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Activities of Daily Living><Activities of everyday life><Acute><Acute Disease><Adult><Adult Human><Age><Antibodies><Antibody Response><Antigenic Determinants><Antigens><Avidity><B blood cells><B cell><B cell repertoire><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Binding Determinants><COVID-19 antibody><COVID-19 infection><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><Cessation of life><Characteristics><Child><Child Care><Child Youth><Childhood><Children (0-21)><Class Switching><Class Switchings><Clinical Treatment Moab><CoV-2><CoV2><Communities><Data Set><Death><Development><Disease><Disease Outcome><Disorder><Enrollment><Epitopes><Evaluation><Fc Receptor><Frequencies><Genes><Genomics><Goals><HIV><HIV Infections><HTLV-III Infections><HTLV-III-LAV Infections><Herd Immunity><Hospital Admission><Hospitalization><Hospitalized Child><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><Ig Somatic Hypermutation><IgG><Immune><Immune response><Immunes><Immunity><Immunogenetics><Immunoglobulin Class Switching><Immunoglobulin Class Switchings><Immunoglobulin G><Immunoglobulin Isotype-Switch Recombination><Immunoglobulin Somatic Hypermutation><Immunoglobulin Switch Recombination><Immunological response><Individual><Infection><Inflammation><Inflammatory><Innate Immunity><Isotype Switching><Isotype Switchings><Kinetics><Knowledge><LAV-HTLV-III><Life><Longitudinal Studies><Lymphadenopathy-Associated Virus><MIS-C><Measures><Memory B Cell><Memory B-Lymphocyte><Messenger RNA><Metabolic Glycosylation><Modernization><Molecular Interaction><Monoclonal Antibodies><Multiorgan Inflammatory Syndrome in Children><Multisystem Inflammatory Syndrome in Children><Native Immunity><Natural Immunity><Nature><Non-Specific Immunity><Nonspecific Immunity><Outcome><Persons><Phenotype><Population><Predisposition><Prevention><Proteins><Puericulture><Resistance><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 antibody><SARS-CoV-2 infection><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 antibody><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><Schools><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 related corona virus 2><Sorting><Specificity><Susceptibility><Switch Recombination><Syndrome><System><Testing><Time><Vaccinated><Vaccination><Vaccines><Variant><Variation><Viral><Virus><Virus-HIV><Work><Wuhan coronavirus><acute disease/disorder><acute disorder><adulthood><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><age 18 years><age dependent><age related><ages><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody dependent cell mediated cytotoxicity><antibody dependent cytotoxicity><antibody mediated cellular cytotoxicity><antibody receptor><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><antibody-dependent cell cytotoxicity><antibody-dependent cellular cytotoxicity><antibody-dependent cellular phagocytosis><antibody-mediated cytotoxicity><biophysical characteristics><biophysical characterization><biophysical measurement><biophysical parameters><biophysical properties><computer based prediction><coronavirus disease 2019 antibody><coronavirus disease 2019 infection><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease-19 virus><daily living function><daily living functionality><deploy vaccines><design><designing><developmental><distribute vaccines><eighteen year old><eighteen years of age><enroll><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><functional ability><functional capacity><glycosylation><hCoV19><host response><immune system response><immunization strategy><immunogen><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><insight><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><long-term study><longitudinal outcome studies><longterm study><mAbs><mRNA><monoclonal Abs><multisystem inflammatory syndrome of children><nCoV2><neutralizing antibody><novel><pandemic><pandemic disease><pathogen><pediatric><pediatric inflammatory multisystem syndrome><post SARS-CoV-2 infection><prediction model><predictive modeling><prevent><preventing><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><protective effect><resistant><respiratory virus><response><school reopening><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 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><somatic hypermutation><vaccination strategy><vaccine deployment><vaccine distribution><vaccine roll-out><vaccine rollout><youngster>