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Principal Investigator: Shane P Crotty
Organization: LA JOLLA INSTITUTE FOR IMMUNOLOGY
Fiscal Year: 2024
Award: $781,696
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY – Project 1
COVID remains a major killer and disruptor worldwide. We made fundamental contributions to the understanding
of COVID and T and B cell immune memory after SARS2 infection and COVID vaccines. Those studies
predominantly examined human blood. In Project 1 we now aim to complement those fundamental findings with
studies of T and B cell memory of URT lymphoid tissue and nasal epithelium. Mechanistic studies, particularly
in humans, are essential to inform on URT immune memory and the roles of long GCs in adaptive immune
responses, but are currently sparse or nonexistent given the complexities for such experiments. Here we address
these important knowledge gaps, synergizing with Project 2 and 3. We will do so through a series of experiments.
Additionally, there are striking data demonstrating that (1) long GCs can exist after acute SARS2 infection, (2)
long GCs can exist after a protein immunization, and (3) long GCs can exist after mRNA vaccination. The recent
recognition of these long GCs to acute antigens significantly changes our understanding of immune responses,
and long GCs appear to have great value for protective immunity and immune memory. We hypothesize that
long GCs have broad impacts on adaptive immunity, including memory B cell affinity maturation, memory B cell
functional properties, the functionality and durability of memory follicular helper T (TFH) cells, and characteristics
of mucosal immunity in the upper airways. All of those attributes are directly examined in this Project. In both
components (analyses of long GCs and analyses of URT immune memory), we will study multiple human
cohorts, with particular focus on COVID-19 breakthrough infections and COVID-19 vaccinations.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Ab response><Acute><Address><Adenoidal structure><Adenoids><Affinity><Antibodies><Antibody Formation><Antibody Production><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Biology><Blood><Blood Reticuloendothelial System><CAIV-T><CD27 Antigens><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><COVID-19><COVID-19 S protein><COVID-19 infection><COVID-19 spike><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 vaccination><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><CV-19><Cell Body><Cell Cycle Kinetics><Cell Kinetics><Cells><Characteristics><Circulation><CoV-2><CoV2><Complement><Complement Proteins><Coronavirus Infectious Disease 2019><Data><Exhibits><FluMist><Frequencies><Germinal Center><Grippe><Human><Immune memory><Immune response><Immunity><Immunization><Immunochemical Immunologic><Immunologic><Immunologic Memory><Immunological><Immunological Memory><Immunological response><Immunologically><Immunologics><Immunology><Infection><Influenza><Intervention><Intervention Strategies><Kinetics><Knowledge><LYT3><Link><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic Tissue><Lymphatic nodes><Lymphoid Tissue><Measures><Memory><Memory B Cell><Memory B-Lymphocyte><Modern Man><Mucosa><Mucosal Immunity><Mucosal Tissue><Mucous Membrane><Nasal Epithelium><Paxlovid><Pharyngeal Tonsil><Phenotype><Population><Property><Proteins><RNA immunization><RNA vaccination><RNA vaccine><RNA-based vaccine><Ritonavir><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S><SARS-CoV-2 S protein><SARS-CoV-2 infection><SARS-CoV-2 spike><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><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-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Series><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 CoV 2 vaccine><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 S protein><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Site><Source><Structure of germinal center of lymph node><Surface><Swab><T memory cell><T-Cell Activation Antigen><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><TNFRSF7 Receptor><Testing><Time><Upper respiratory tract><Vaccination><Vaccines><Virus><Wuhan coronavirus><acute COVID-19><acute SARS-CoV-2 infection><acute phase of COVID-19><acute phase of SARS-CoV-2 infection><adaptive immune response><adaptive immunity><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><analyzing longitudinal><anamnestic reaction><antibody biosynthesis><booster dose><booster shot><booster vaccine><breakthrough infection><cohort><complementation><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 infection><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 vaccination><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus infectious disease-19><experiment><experimental research><experimental study><experiments><flu infection><flu virus infection><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by 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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><respiratory pathogen><response><secondary immune response><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><social role><spike proteins on SARS-CoV-2><thymus derived lymphocyte><upper airway tract><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><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine boost><vaccine candidates against SARS-CoV-2><vaccine for novel coronavirus><vaccines preventing COVID><vaccines to prevent COVID><viral pathogen><virus pathogen>