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Principal Investigator: Julia Meghan Davis-Porada
Organization: COLUMBIA UNIVERSITY HEALTH SCIENCES
Fiscal Year: 2023
Award: $49,170
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
Vaccines save lives, and the rapid development of novel vaccines against severe acute respiratory syndrome
coronavirus-2 (SARS-CoV-2) was a triumph for the medical community. While the rapid deployment of these
vaccines has undoubtedly attenuated the severe morbidity and mortality induced by the virus, their efficacy is
decreased against variant strains, in children, and with increasing time post-administration. These clinical
findings highlight our lack of understanding of how durable, protective immunity is induced by vaccination and
how this varies across the population. Studying vaccine induced memory in humans has two major challenges.
First, viral exposures over life confound the identification of vaccine-specific memory; second, the stores of
memory lymphocytes reside in the tissues, which makes monitoring the vaccine response in healthy individuals
challenging. The SARS-CoV-2 pandemic affords us the unique opportunity to study the response to a novel
vaccine formulation without confounding natural antigenic exposure and the ability to distinguish infection from
vaccination by serology. Additionally, our unique organ donor tissue resource provides a validated model to
investigate tissue-localized vaccine-specific immunity. The goal of this proposal is to understand how vaccine-
induced immune memory is distributed across tissue and affected by host factors such as age. The central
hypothesis of this proposal is that induction and maintenance of vaccine-specific memory is controlled in
lymph nodes, and specific early induction events directly impact immune memory development and
vary with age. I will address this hypothesis and meet the goals of the study by using flow cytometry and high-
dimensional sequencing to evaluate the relationship between circulating and tissue-localized vaccine memory
and how they differ in phenotype, function, and across age. I will also investigate how the initial, inflammatory
host-specific response to the mRNA-1273 vaccine differs across age and correlates to the quantity of immune
memory induced. The results of this study will elucidate the importance of lymph nodes in the vaccine
response and highlight the benefits and downfalls of mRNA vaccines across various host factors. These
results will have implications for future vaccine design and may play a role in managing both the SARS-CoV-2
pandemic and any future ones.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><21+ years old><Ab response><Adult><Adult Human><Affect><Age><Antibody Formation><Antibody Production><Antibody titer measurement><Attenuated><Authorization><Authorization documentation><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Blood><Blood Reticuloendothelial System><Blood Sample><Blood specimen><Body Tissues><COVID><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 public health crisis><COVID-19 vaccine><COVID-19 virus><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 pandemic><COVID19 public health crisis><COVID19 vaccine><COVID19 virus><Cell Body><Cell Function><Cell Process><Cell physiology><Cells><Cellular Function><Cellular Physiology><Cellular Process><Child><Child Youth><Children (0-21)><Clinical><CoV disease><CoV-2><CoV2><Collaborations><Communities><Data><Development><ELISA><Enzyme-Linked Immunosorbent Assay><Event><Exhibits><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Frequencies><Future><Goals><Health><Host Factor><Host Factor Protein><Human><Humoral Immunities><IFN><Immune><Immune memory><Immune response><Immune system><Immunes><Immunity><Immunologic Memory><Immunological Memory><Immunological response><Individual><Infection><Inflammatory><Innate Immunity><Integration Host Factors><Interferons><Investigation><Knowledge><Laboratories><Life><Lung><Lung Respiratory System><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic Tissue><Lymphatic cell><Lymphatic nodes><Lymphocyte><Lymphocytic><Lymphoid><Lymphoid Tissue><Macrophage><Maintenance><Measures><Mediating><Medical><Memory><Memory B Cell><Memory B-Lymphocyte><Modeling><Modern Man><Moderna COVID-19 vaccine><Moderna coronavirus disease 2019 vaccine><Monitor><Mononuclear><Morbidity><Morbidity - disease rate><Mucosa><Mucosal Tissue><Mucous Membrane><Mφ><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Organ Donor><Organ Procurements><Outcome><Permission><Persons><Phenotype><Population><Preventative strategy><Prevention strategy><Preventive strategy><Production><Property><Proteins><RNA vaccine><RNA-based vaccine><Research Resources><Residencies><Resources><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 epidemic><SARS-CoV2 pandemic><SARS-CoV2 vaccine><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><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 CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><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 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Site><Spatial Distribution><Subcellular Process><T memory cell><T-Cells><T-Lymphocyte><Time><Tissue Donors><Tissues><Vaccinated><Vaccination><Vaccine Design><Vaccinee><Vaccines><Variant><Variation><Viral><Viral Diseases><Virus><Virus Diseases><Work><Wuhan coronavirus><adaptive immunity><adulthood><ages><anamnestic reaction><antibody biosynthesis><antibody titering><antibody-based immunity><attenuate><attenuates><authority><corona virus disease><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><coronavirus disease><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus 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vaccines><pandemic><pandemic disease><pathogen><present pandemic><prevent><preventing><pulmonary><quantitative imaging><respiratory virus><response><secondary immune response><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 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><social role><thymus derived lymphocyte><tissue resource><unvaccinated><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination study><vaccination trial><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine deployment><vaccine development><vaccine distribution><vaccine efficacy><vaccine for novel coronavirus><vaccine formulation><vaccine response><vaccine responsiveness><vaccine roll-out><vaccine rollout><vaccine strategy><vaccine study><vaccine trial><vaccine-induced immunity><vaccine-induced protection><vaccine-induced response><vaccinology><viral infection><virus infection><virus-induced disease><youngster>