Project-002

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

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Principal Investigator: Suresh B Boppana
Organization: UNIVERSITY OF ALABAMA AT BIRMINGHAM
Fiscal Year: 2022
Award: $270,527
Funding agency: National Cancer Institute

Project Summary/Abstract
The novel coronavirus SARS-CoV-2 (SARS2) pandemic has so far infected greater than 65 million
individuals and resulted in almost 850,000 deaths in the US. Although it has been suggested that
adaptive immunity plays an important role in improving clinical outcomes of patients infected with
SARS2, correlates of protective immune responses have not been defined. Also, an explanation for the
variability in clinical disease and outcome in patients with SARS2 infection has not been explained
based on qualitative and quantitative antiviral immune responses. Studies in immunocompromised
adults have shown somewhat decreased efficacy of SARS2 mRNA vaccines and increased rates of
breakthrough infections. A significant proportion of children with deficits in immune competence
secondary to cancer chemotherapy and hematologic disorders were observed to have blunted antiviral
antibody responses following SARS2 infection and shed virus for prolonged periods of time (>6 weeks)
in the upper respiratory tract. Together, these findings raise the possibility that children with specific
qualitative or quantitative deficits in adaptive immunity may generate somewhat blunted or decreased
immune responses to SARS2 vaccines. The safety and immunogenicity of SARS2 mRNA vaccine in
young children especially those with compromised immune responses have not been examined. The
objective of the proposed study is to define quantitative and qualitative antiviral antibody responses and
T cell immunity responses generated following SARS2 mRNA vaccination in a cohort of children with
varying levels immune responsiveness and compare those with age-match healthy children. Defining
relationships between variations in immune competence and vaccine-mediated protection could provide
a novel insight into the level and nature of adaptive immunity that can produce robust immune
responses to SARS2 mRNA vaccine. Our studies will also determine the safety of SARS2 mRNA
vaccine in children with impaired immunity and in a group of healthy children. Analysis of the quality and
quantity of SARS2 antibody and T cell responses to the mRNA vaccine will help develop vaccine
candidates or adapt existing vaccines to provide effective protection. In addition, the proposed studies
will also examine the durability of vaccine-mediated immunity and the need for additional doses that can
protect this vulnerable group of children.

Terms: <0-11 years old><11 year old><11 years of age><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><21+ years old><ACE2><Active Follow-up><Adult><Adult Human><Adverse Experience><Adverse effects><Adverse event><Age><Alabama><Antibodies><Antibody Response><Antigens><Appointment><Assay><B.1.617.2><Binding><Bioassay><Biologic Assays><Biological Assay><Blood Diseases><Blood Sample><Blood Serum><Blood specimen><COVID><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 antibody><COVID-19 associated death><COVID-19 associated fatality><COVID-19 associated mortality><COVID-19 crisis><COVID-19 death><COVID-19 detection><COVID-19 epidemic><COVID-19 exposure><COVID-19 fatality><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 induced death><COVID-19 induced fatality><COVID-19 induced mortality><COVID-19 infection><COVID-19 mortality><COVID-19 pandemic><COVID-19 predisposition><COVID-19 public health crisis><COVID-19 related death><COVID-19 related fatality><COVID-19 related mortality><COVID-19 susceptibility><COVID-19 vaccine><COVID-19 virus><COVID-19 vulnerability><COVID19><COVID19  detection><COVID19 associated death><COVID19 associated fatality><COVID19 associated mortality><COVID19 crisis><COVID19 death><COVID19 epidemic><COVID19 fatality><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 induced death><COVID19 induced fatality><COVID19 induced mortality><COVID19 infection><COVID19 mortality><COVID19 pandemic><COVID19 public health crisis><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 vaccine><COVID19 virus><CV-19><CV19><Cancers><Cardiac><Cardiac Toxicity><Cardiology><Cardiotoxic><Cardiotoxicity><Case Report Form><Cessation of life><Chemotherapy Protocol><Chemotherapy Regimen><Chemotherapy-Oncologic Procedure><Child><Child Health><Child Youth><Childhood><Children (0-21)><Clinic><Clinical><Clinical Sciences><CoV disease><CoV emergence><CoV-2><CoV2><Combination Chemotherapy Regimen><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 susceptibility><Coronavirus disease 2019 vulnerability><Data><Death><Delta variant><Disease><Disease Outcome><Disorder><Dose><Effectiveness><Enrollment><Evaluation><Faculty><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Hb SS disease><HbSS disease><Hematologic Diseases><Hematological Disease><Hematological Disorder><Hematology><Hemoglobin S Disease><Hemoglobin sickle cell disease><Hemoglobin sickle cell disorder><Hospital Admission><Hospitalization><Immune><Immune Modulation Therapy><Immune response><Immune system><Immunes><Immunity><Immunization><Immunochemical Immunologic><Immunocompetence><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunologic><Immunologic Competence><Immunologic Sensitization><Immunologic Stimulation><Immunological><Immunological Competence><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunologically><Immunologics><Immunostimulation><Immunosuppressed Host><Impairment><Individual><Infrastructure><Laboratories><Link><Malignant Neoplasms><Malignant Tumor><Masks><Measurement><Measures><Mediating><Messenger RNA><Molecular Interaction><Monitor><Myocarditis><Nature><Non-Polyadenylated RNA><Organ><PBMC><Participant><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pediatric Oncology><Pediatrics><Pericarditis><Peripheral Blood Mononuclear Cell><Play><Policies><Population><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Primary Care><Primary Health Care><Primary Healthcare><Pulmonary Body System><Pulmonary Organ System><Quimioterapia><RNA><RNA Gene Products><RNA immunization><RNA vaccination><RNA vaccine><RNA-based vaccine><Recommendation><Reporter><Reporting><Research><Research Specimen><Respiratory System><Respiratory Tracts><Respiratory tract structure><Ribonucleic Acid><Risk><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 B.1.617.2><SARS-CoV-2 antibody><SARS-CoV-2 associated death><SARS-CoV-2 associated fatality><SARS-CoV-2 associated mortality><SARS-CoV-2 death><SARS-CoV-2 delta><SARS-CoV-2 detection><SARS-CoV-2 epidemic><SARS-CoV-2 exposure><SARS-CoV-2 fatality><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 induced death><SARS-CoV-2 induced fatality><SARS-CoV-2 induced mortality><SARS-CoV-2 infection><SARS-CoV-2 mortality><SARS-CoV-2 pandemic><SARS-CoV-2 predisposition><SARS-CoV-2 related death><SARS-CoV-2 related fatality><SARS-CoV-2 related mortality><SARS-CoV-2 susceptibility><SARS-CoV-2 vaccine><SARS-CoV-2 vulnerability><SARS-CoV2><SARS-CoV2 antibody><SARS-CoV2 epidemic><SARS-CoV2 exposure><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-CoV2 vaccine><SARS-associated corona virus 2><SARS-associated 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coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 predisposition><Severe acute respiratory syndrome coronavirus 2 susceptibility><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome coronavirus 2 vulnerability><Severe acute respiratory syndrome related corona virus 2><Sickle Cell Anemia><Social Distance><Solid><Specimen><Standardization><Symptoms><T cell response><T-Cells><T-Lymphocyte><Teen><Teenagers><Time><Translational Research><Translational Science><Troponin><Upper respiratory tract><Vaccinated><Vaccination><Vaccines><Variant><Variation><Viral><Viral Antibodies><Viral Shedding><Virus><Virus Shedding><Visit><Vulnerable Populations><Wuhan coronavirus><active followup><adaptive immunity><adult youth><adulthood><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after severe acute respiratory distress syndrome CoV-2 infection><age 11 years><age group><ages><allergic/immunologic body system><allergic/immunologic organ system><angiotensin converting enzyme 2><angiotensin converting enzyme II><anti-viral antibody><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><antiviral antibody><base><blood disorder><breakthrough infection><cancer chemotherapy><cardiac inflammation><chemotherapy><clinical care><clinical center><cohort><comparator group><comparison group><corona virus disease><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><corona virus emergence><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 antibody><coronavirus disease 2019 associated death><coronavirus disease 2019 associated fatality><coronavirus disease 2019 associated mortality><coronavirus disease 2019 crisis><coronavirus disease 2019 death><coronavirus disease 2019 detection><coronavirus disease 2019 epidemic><coronavirus disease 2019 exposure><coronavirus disease 2019 fatality><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 induced death><coronavirus disease 2019 induced fatality><coronavirus disease 2019 induced mortality><coronavirus disease 2019 infection><coronavirus disease 2019 mortality><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 related death><coronavirus disease 2019 related fatality><coronavirus disease 2019 related mortality><coronavirus disease 2019 vaccine><coronavirus 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CoV><emerging corona virus><emerging coronavirus><enroll><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><fatality due to COVID-19><fatality due to COVID19><fatality due to SARS-CoV-2><fatality due to coronavirus disease 2019><fatality due to severe acute respiratory syndrome coronavirus 2><flow cytophotometry><follow up><follow-up><followed up><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following severe acute respiratory distress syndrome CoV-2 infection><followup><hCoV19><host response><immune modulating therapies><immune modulatory therapies><immune system response><immune-modulation treatment><immunogen><immunogenicity><immunomodulation therapy><immunomodulation treatment><immunomodulatory therapies><immunomodulatory therapy><immunomodulatory treatment><immunoresponse><immunosuppressed patient><improved><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><infection rate><insight><mRNA><mRNA immunization><mRNA vaccination><mRNA vaccine><mRNA-based vaccine><malignancy><mortality due to COVID-19><mortality due to COVID19><mortality due to SARS-CoV-2><mortality due to coronavirus disease 2019><mortality due to severe acute respiratory syndrome coronavirus 2><nCoV><nCoV2><nasal swab><neoplasm/cancer><new CoV><new corona virus><new coronavirus><novel><novel CoV><novel corona virus><novel coronavirus><pandemic><pandemic disease><particle><pediatric><peripheral blood><post SARS-CoV-2 infection><predisposed to Coronavirus disease 2019><prevent><preventing><previous COVID-19 infection><previous SARS-CoV-2 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><prospective><rate of infection><respiratory><response><sample collection><seasonal coronavirus><severe acute respiratory syndrome coronavirus 2 B.1.617.2><severe acute respiratory syndrome coronavirus 2 antibody><severe acute respiratory syndrome coronavirus 2 associated death><severe acute respiratory syndrome coronavirus 2 associated fatality><severe acute respiratory syndrome coronavirus 2 associated mortality><severe acute respiratory syndrome coronavirus 2 death><severe acute respiratory syndrome coronavirus 2 detection><severe acute respiratory syndrome coronavirus 2 fatality><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 induced death><severe acute respiratory syndrome coronavirus 2 induced fatality><severe acute respiratory syndrome coronavirus 2 induced mortality><severe acute respiratory syndrome coronavirus 2 mortality><severe acute respiratory syndrome coronavirus 2 related death><severe acute respiratory syndrome coronavirus 2 related fatality><severe acute respiratory syndrome coronavirus 2 related mortality><sickle cell disease><sickle cell disorder><sickle disease><sicklemia><social role><specimen collection><susceptible to COVID-19><susceptible to Coronavirus disease 2019><susceptible to SARS-CoV-2><susceptible to Severe acute respiratory syndrome coronavirus 2><teen years><teenage><telehealth><thymus derived lymphocyte><translation research><upper airway tract><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 candidate><vaccine development><vaccine efficacy><vaccine for novel coronavirus><vulnerable group><vulnerable people><young adult><young adulthood><youngster>