Vaccine and Infection Induced Immunity in the Young and Aged

Document text

Principal Investigator: Rafi  Ahmed
Organization: EMORY UNIVERSITY
Fiscal Year: 2024
Award: $1,864,381
Funding agency: National Institute of Allergy and Infectious Diseases

The overarching goal of our CCHI application on “Vaccine and Infection Induced Immunity in the Young and
Aged” is to address fundamental issues about innate and adaptive immunity in humans to infection and
vaccination. Our proposal is focused around a large cohort of > 700 COVID-19 patients that we have been
following for the past 3 years and now propose to follow for an additional 5 years during the course of this
proposal. These patients were recruited at our two clinical research sites, Emory University (Atlanta, Georgia)
and Fred Hutchinson Cancer Center (Seattle, Washington). Our combined cohort of > 700 patients consists of
individuals who were first infected with SARS-CoV-2 and then received the mRNA Pfizer or Moderna vaccine,
and some individuals who got the vaccine first and were then infected. Several of these individuals then had
booster shots and some also had breakthrough infections. During this 3 year period of multiple antigen
encounters we have collected on average between 5-10 blood samples from each patient. We now propose to
collect 3-4 samples/year from each patient for the next 5 years. The longitudinal assessment of innate, humoral
and cellular immunity in this large cohort over an 8 year period with 20-30 time points for each person will provide
an extraordinary and unprecedented look at the durability and evolution adaptive and innate immunity following
infection and vaccination. These studies will not only provide insight into the underlying mechanisms of innate
immunity and long-term immune memory but will also inform how we develop optimal vaccination strategies
against SARS-CoV-2 and other emerging viral infections. We have assembled a group of outstanding
investigators from five institutions with highly complementary expertise and organized our renewal application
along the following Projects and Cores: Project 1: Immune Memory: Drs. Rafi Ahmed and Julie McElrath; Project
2: Innate Immunity: Drs. Bali Pulendran and Donna Farber; Project 3: immune Senescence: Dr. Jorg Goronzy;
Core A: Administrative: Dr. Rafi Ahmed; Core B: Genomics Core: Drs. Steve Bosinger and William Greenleaf;
Core C: Clinical and Biostatistics: Drs. Sri Edupuganti, Julie McElrath, Max Lau, and Veronika Zarnitsyna. The
overall broad Aims of our CCHI program are as follows: Aim 1: Longitudinal analysis of T and B cell responses
to SARS-CoV-2. Aim 2: Innate Immunity with focus on functional and epigenetics changes in myeloid cells.
Aim 3: Effect of aging on SARS-CoV-2 T cell responses.

Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Address><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Biometrics><Biometry><Biostatistics><Blood Sample><Blood specimen><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 Mediated Immunology><Cell-Mediated Immunity><Cellular Immunity><Clinical><CoV-2><CoV2><Coronavirus Infectious Disease 2019><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Evolution><Genomics><Goals><Human><Humoral Immunities><Immune memory><Immunity><Immunologic Memory><Immunological Memory><Individual><Infection><Innate Immunity><Institution><Investigators><Memory B Cell><Memory B-Lymphocyte><Messenger RNA><Modern Man><Myeloid Cells><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Patients><Persons><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><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 response><T-Cells><T-Lymphocyte><Time><Universities><Vaccination><Vaccines><Viral Diseases><Virus Diseases><Washington><Wuhan coronavirus><adaptive immunity><age associated effects><age effect><age related effects><aged><aging effect><analyzing longitudinal><anamnestic reaction><antibody-based immunity><booster dose><booster shot><booster vaccine><breakthrough infection><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><hCoV19><immune senescence><immunization strategy><immunogen><immunosenescence><impact of age><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><influence of age><insight><longitudinal analysis><mRNA><nCoV2><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><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><thymus derived lymphocyte><vaccination strategy><vaccine boost><viral infection><virus infection><virus-induced disease>