PROJECT 1: IMMUNE MEMORY

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

Document text

Principal Investigator: Rafi  Ahmed
Organization: EMORY UNIVERSITY
Fiscal Year: 2024
Award: $673,340
Funding agency: National Institute of Allergy and Infectious Diseases

Our long-term goal is to understand the cellular and molecular basis of immunological memory in humans. We
will address this important question in Project 1 by doing a detailed analysis of both humoral and cellular immunity
in a longitudinal cohort of over > 700 COVID-19 patients that we have been following for the past three years
and will now follow for another five years. These patients were recruited at our two clinical sites located in Atlanta
(Emory University) and Seattle (Fred Hutchinson Cancer Center). This combined cohort consists of individuals
who were first infected with SARS-CoV-2 and then got the Pfizer or Moderna mRNA vaccine, and some
individuals who received the vaccine first and then got infected. Many of these individuals have then gotten
booster shots with the vaccine and several of them have also had additional breakthrough infections. During this
three-year period of multiple antigen encounters of various combinations of infection and vaccination, we have
collected between 5-10 longitudinal blood samples from each patient. We now propose to follow these patients
for another five years and will collect 3-4 samples per year from each patient. Thus, we will have 20-30
longitudinal blood samples from each patient over an 8-year period. In addition, in the next five years we will also
collect bone marrow aspirates and mucosal samples from a subset of these individuals. The Specific Aims of
Project 1 are as follows: Aim 1: To determine the magnitude and durability of humoral and cellular immunity in
the entire cohort of > 700 COVID-19 patients over a period of 8 years. Aim 2: To examine the evolution of
memory B cell responses and determine the longevity of bone marrow plasma cells. Aim 3. To track
differentiation of T cells over time and define the transcriptional and epigenetic signatures of virus specific
memory CD8 and CD4 T cells.

Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Antibody Response><Antigens><BMCELLTY><Binding><Biostatistics Core><Blood Plasma Cell><Blood Sample><Blood specimen><Bone Marrow><Bone Marrow Aspiration><Bone Marrow Cellularity><Bone Marrow Reticuloendothelial System><Booster Immunization><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><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 infected patient><COVID patient><COVID positive patient><COVID-19><COVID-19 infected patient><COVID-19 infection><COVID-19 patient><COVID-19 positive patient><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 virus><CV-19><Cancer Center><Cell Differentiation><Cell Differentiation process><Cell Mediated Immunology><Cell-Mediated Immunity><Cellular Immunity><Clinical><CoV-2><CoV2><Collaborations><Coronavirus Infectious Disease 2019><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Evolution><Gene Transcription><Genetic Transcription><Genomics><Goals><Human><Humoral Immunities><Immune memory><Immunity><Immunologic Memory><Immunological Memory><Immunology><Individual><Infection><Innate Immunity><Institution><Investigators><Knowledge><LYT3><Length of Life><Long-term cohort><Longevity><Longitudinal cohort><Longterm cohort><Memory><Memory B Cell><Memory B-Lymphocyte><Modern Man><Molecular><Molecular Interaction><Mucosa><Mucosal Tissue><Mucous Membrane><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Patients><Phenotype><Plasma Cells><Plasmacytes><RNA Expression><RNA vaccine><RNA-based vaccine><Research Personnel><Researchers><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><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><Sampling><Secondary Immunization><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><T cell differentiation><T-Cells><T-Lymphocyte><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><Time><Transcription><Universities><Vaccination><Vaccines><Viral Diseases><Virus><Virus Diseases><Wuhan coronavirus><adaptive immune response><aged><anamnestic reaction><antibody-based immunity><booster dose><booster shot><booster vaccination><booster vaccine><breakthrough infection><cellular differentiation><clinical research site><clinical site><cohort><coronavirus disease 2019><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><epigenetically><experience><hCoV19><immune senescence><immunization strategy><immunogen><immunosenescence><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><mRNA vaccine><mRNA-based vaccine><memory CD4 T cell><memory CD4 T lymphocyte><nCoV2><neutralizing antibody><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><plasmocyte><programs><recruit><response><secondary immune response><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><success><thymus derived lymphocyte><translational study><vaccination strategy><vaccine boost><variants of concern><viral infection><virus infection><virus-induced disease>