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Principal Investigator: ARTHUR Y KIM
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2024
Award: $364,178
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Translational research is critically dependent on availability of adequate specimens from well-defined clinical
cohorts of patients. This Clinical Core builds and maintains such cohorts and facilitates a broad array of studies
in human immunology. During the past three cycles of our consortium, we successfully recruited and enrolled
over two thousand subjects, leveraging two paradigm-shifting therapeutic advances of this century: effective
direct-acting antivirals (DAAs) against hepatitis C virus (HCV) and immune checkpoint inhibitors (ICIs),
particularly targeting the PD-1 axis, for cancer. These developments allowed unique opportunities to study the
scars left by human chronic viral infection and to explore the reversal of T-cell exhaustion and resetting of
immunity. We can further capitalize on “the human experiment” by dissecting immune mechanisms in humans
where a single immune pathway involved in the germinal center response can be interrogated by capturing
standard of care vaccination in patients receiving αPD-1. Finally, during the last cycle a global immunological
challenge in the COVID-19 pandemic spurred a third major advance of this century: the introduction of SARS-
CoV-2 mRNA vaccines. While their biology and clinical courses differ, SARS-CoV-2 and HCV are each RNA
viruses where immune responses and outcomes can be compared. Moreover, we can dissect differences
between immune responses to vaccination for Flu and SARS-CoV-2. Samples collected by the Clinical Core
will allow examination of three areas of immunobiology: 1) investigation of persisting virus and immune
dysfunction in post-acute sequelae of PASC; 2) interrogation of immune scarring after cure of a persisting
infection, and 3) dissection of an immunoregulatory pathway associated with persisting infections for its role in
vaccine-induced adaptive immune memory. Integration of findings across these areas is a distinct advantage of
this Immune Perturbation Study Group (IPSG), empowered by this Clinical Core and its relevant cohorts and
large numbers of well-annotated samples. By supporting the studies described in the Projects and the Immune
Health Core, this Core will facilitate a novel and integrated examination of human immune responses to viral
pathogens and to their vaccines in the context of three key perturbations: PASC, HCV infection and specific
immune manipulation via αPD-1.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Abscission><Acute><Affect><Animal Model><Animal Models and Related Studies><Anti-viral Agents><Area><Biology><Blood><Blood Plasma><Blood Reticuloendothelial System><Blood Serum><Body Tissues><COVID crisis><COVID epidemic><COVID infected patient><COVID pandemic><COVID patient><COVID positive patient><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infected patient><COVID-19 pandemic><COVID-19 patient><COVID-19 period><COVID-19 positive patient><COVID-19 public health crisis><COVID-19 virus><COVID-19 years><COVID19 patient><COVID19 positive patient><COVID19 virus><Cancers><Catalogs><Cell Body><Cells><Checkpoint inhibitor><Chronic><Cicatrix><Clinical><Clinical Data><CoV-2><CoV2><Collection><Cross Sectional Analysis><Cross-Sectional Analyses><Cross-Sectional Studies><Cross-Sectional Survey><Data><Data Bases><Databases><Development><Disease Frequency Surveys><Dissection><Drug or chemical Tissue Distribution><Enrollment><Excision><Extirpation><Face><Filamentous Fungi><Flu vaccination><Generations><Germinal Center><Goals><HBV><HCV><HCV infection><Hepatitis B Virus><Hepatitis C><Hepatitis C virus><Hepatitis C virus infection><Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted><Hepatitus C><History><Homologous Serum Hepatitis Virus><Human><Immune><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune checkpoint inhibitor><Immune mediated therapy><Immune memory><Immune response><Immune system><Immunes><Immunity><Immunobiology><Immunochemical Immunologic><Immunodeficiency and Immunosuppression Disorders><Immunologic><Immunologic Diseases><Immunologic Memory><Immunological><Immunological Diseases><Immunological Dysfunction><Immunological Memory><Immunological System Dysfunction><Immunological response><Immunologically><Immunologically Directed Therapy><Immunologics><Immunology><Immunomodulation><Immunophysiology><Immunotherapy><Infection><Influenza Vaccines><Influenza immunization><Influenza vaccination><Infrastructure><Investigation><Investigators><Left><Liver><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic nodes><Malignant Neoplasms><Malignant Tumor><Measures><Modern Man><Molds><Nature><Outcome><PASC><PBMC><PD 1><PD-1><PD-1 blockade><PD-1 checkpoint pathway><PD-1 pathway><PD-1 signaling pathway><PD1><PD1 blockade><PD1 checkpoint pathway><PD1 pathway><PD1 signaling pathway><Pathway interactions><Patient Recruitments><Patients><Peripheral Blood Mononuclear Cell><Plasma><Plasma Serum><Post Acute Sequelae of COVID19><Post Acute Sequelae of SARS-CoV-2><Post Acute Sequelae of SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Prophylactic vaccination against influenza><RNA Viruses><RNA vaccine><RNA-based vaccine><Recording of previous events><Removal><Research><Research Personnel><Research Resources><Research Specimen><Researchers><Resources><Reticuloendothelial System, Serum, Plasma><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 infected patient><SARS-CoV-2 pandemic><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Scars><Serology><Serum><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-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 related corona virus 2><Specimen><Standardization><Structure of germinal center of lymph node><Surgical Removal><T-Cells><T-Lymphocyte><Therapeutic><Tissue Banks><Tissue Collection><Tissue Distribution><Tissue Sample><Tissue repository><Tissues><Translating><Translational Research><Translational Science><Vaccination><Vaccines><Viral Diseases><Virus><Virus Diseases><Wuhan coronavirus><aPD-1><aPD1><adverse sequelae of COVID><adverse sequelae of COVID-19><adverse sequelae of coronavirus disease><adverse sequelae of coronavirus disease 2019><analyzing longitudinal><anamnestic reaction><anti programmed cell death 1><anti programmed cell death protein 1 checkpoint pathway><anti programmed cell death protein 1 pathway><anti programmed cell death protein 1 signaling pathway><anti-PD-1><anti-PD-1 blockade><anti-PD1><anti-PD1 blockade><anti-programmed cell death protein 1><anti-viral compound><anti-viral drugs><anti-viral medication><anti-viral therapeutic><anti-virals><antiPD-1><antiPD1><biobank><biorepository><catalog><chronic COVID-19 sequelae><chronic infection><clinical relevance><clinically relevant><cohort><compare to control><comparison control><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 infected patient><coronavirus disease 2019 pandemic><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 public health crisis><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease infected patient><coronavirus disease pandemic><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus patient><data base><depository><design><designing><developmental><empowerment><enroll><exhaustion><experiment><experimental research><experimental study><experiments><faces><facial><flu immunisation><flu vaccine><flu virus vaccine><hCoV19><healing><hep C><hepatic body system><hepatic organ system><hepatitis non A non B><histories><host response><human tissue><immune check point inhibitor><immune health><immune modulation><immune regulation><immune response to vaccination><immune response to vaccines><immune system health><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><infection by hepatitis c virus><influenza virus vaccination><influenza virus vaccine><insight><long haul sequelae of COVID-19><long haul sequelae of coronavirus disease 2019><long-term sequelae of COVID-19><long-term sequelae of SARS-CoV-2><long-term sequelae of coronavirus disease 2019><long-term sequelae of severe acute respiratory syndrome coronavirus 2><longitudinal analysis><lymph gland><lymph nodes><lymphnodes><mRNA vaccine><mRNA-based vaccine><malignancy><model of animal><nCoV2><neoplasm/cancer><non A, non B hepatitis><non-A, non-B hepatitis><novel><participant recruitment><pathogenic virus><pathway><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><persistent infection><post COVID-19 sequelae><post acute sequelae following COVID-19><post-acute sequelae following SARS-CoV-2 infection><post-acute sequelae of COVID-19><post-acute sequelae of acute COVID infection><post-acute sequelae of coronavirus disease 2019><programmed cell death 1><programmed cell death protein 1><programmed death 1><recruit><repository><resection><response><sample collection><secondary immune response><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><sle2><social role><specimen collection><standard of care><systemic lupus erythematosus susceptibility 2><thymus derived lymphocyte><translation research><translational investigation><vaccination against influenza><vaccine against flu><vaccine against influenza><vaccine associated immune response><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><viral infection><viral pathogen><virus infection><virus pathogen><virus-induced disease><αPD-1><αPD1>