Document text
Principal Investigator: James D Brien
Organization: UNIVERSITY OF PUERTO RICO MED SCIENCES
Fiscal Year: 2024
Award: $812,000
Funding agency: National Cancer Institute
SUMMARY/ABSTRACT
Although more than four years have passed since the initial virus appearance, nowadays, most of the population has been
vaccinated with multiple doses of mRNA-based vaccines and has endured multiple infection events. Still, SARS-CoV-2
continues to cause disproportionately higher morbidity and mortality in older adults from these communities, especially in
the Latino-origin population and other vulnerable populations like the hematopoietic stem cell transplants (HSCT)
population. As newer versions of vaccines are adapted to recent SARS-CoV-2 variants (i.e., bivalent vaccines andXBB1.5),
we must continue to determine how effective these vaccines are overtime against emerging variants and establish how those
populations are still responding. We will characterizes the kinetics, magnitude, and durability of type-specific neutralizing
antibody and T cells responses to different current SARS-CoV-2 variants after natural infection or vaccination, designed to
reveal correlates associated with protective immunity or disease severity or progression to long COVID. We pursue to
implement the following new tasks: AIM 1: Task 1.3. Implementation of a third Community Assessment for Public Health
Emergency Response (CASPER) approach, we expect to collect about 2,000 new samples to expand the IDRB. During
prior funding periods, we also supported CASPER I and II. AIM 2: Task 2.5: To evaluate the current anti-SARS-Cov-2 IgG
levels in the population of Puerto Rico following the Community Assessment for Public Health Emergency Response
(CASPER) approach. Task 2.6: characterizes the kinetics, magnitude, and durability of type-specific neutralizing antibody
responses to different current SARS-CoV-2 variants designed to reveal correlates associated with protective immunity. Task
2.7: Supported in our prior findings, we propose determining whether such IgG4 levels induced by mRNA vaccination
could be associated with persistent COVID-19 symptoms (Long-COVID) in our population. Task 2.8: Interrogation of the
Antigen-Specific B Cell Response as described below in the approach section. Task 2.9: Breakthrough SARS-CoV-2
Infections: Investigate the relationship between breakthrough infections, vaccine immunogenicity, and long COVID
symptomatology by actively monitoring HSCT patients. AIM3: Task 3.2: Expand the Innate and Adaptive Immune
Response characterization in underrepresented populations: Investigate the phenotype and function of antigen-specific T
cells, including TFH cells, which support antigen-specific B cell responses. Measure CD4 TFH cells' ability to support
antigen-specific B cell antibody secretion using in vitro CD4-B cell cultures. Task 3.3: Define factors responsible for
decreased T cell help leading to altered antigen-specific antibody responses in patients with HSCTs. AIM 4: Task 4.3: We
will continue to focus on sequencing the circulating and emerging strains and variants and correlating them with the
immunological profile characterized under the new tasks in aims 1 to 3.
We will continue with our efforts directed to guarantee a proper representation of age, sex, gender, and socioeconomic
status as well as individuals with comorbidities including but not limited to obesity, cancer, and autoimmune diseases.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><7S Gamma Globulin><African American><Afro American><Afroamerican><Age><Antibodies><Antibody Response><Antibody titer measurement><Antibody-Secreting Cells><Antigens><Appearance><Area><Autoimmune Diseases><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><B.1.1.529><B.1.617.2><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><COVID disease severity><COVID severity><COVID-19 antibody><COVID-19 antigen><COVID-19 disease severity><COVID-19 exposure><COVID-19 infection><COVID-19 pandemic affected><COVID-19 pandemic consequence><COVID-19 pandemic effects><COVID-19 pandemic impact><COVID-19 pandemic impacted><COVID-19 severity><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19 disease severity><COVID19 infection><COVID19 severity><COVID19 virus><Cancers><Cell Body><Cell Culture Techniques><Cells><CoV-2><CoV2><Communicable Diseases><Communities><Delta variant><Development><Diagnostic><Disease Outcome><Disease Progression><Dissection><Document Type><Dose><Emergency response><Evaluation><Event><Formulation><Funding><Gender><Groups at risk><HSC transplantation><Hematopoietic Stem Cell Transplant><Hematopoietic Stem Cell Transplantation><Hispanic><IgG><IgG4><Immune><Immune mediated therapy><Immune response><Immunes><Immunity><Immunochemical Immunologic><Immunoglobulin G><Immunoglobulin-Secreting Cells><Immunologic><Immunological><Immunological response><Immunologically><Immunologically Directed Therapy><Immunologics><Immunotherapy><In Vitro><Individual><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Kinetics><Latino><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Malignant Neoplasms><Malignant Tumor><Measures><Memory><Monitor><Morbidity><Morbidity - disease rate><Obesity><Omicron variant><Patients><People at risk><Peptides><Persons at risk><Phenotype><Population><Populations at Risk><Prevalence><Puerto Rico><RNA immunization><RNA vaccination><RNA vaccine><RNA-based vaccine><Report (document)><Reporting><Research><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 B.1.1.529><SARS-CoV-2 B.1.617.2><SARS-CoV-2 antibody><SARS-CoV-2 antigen><SARS-CoV-2 delta><SARS-CoV-2 disease severity><SARS-CoV-2 exposure><SARS-CoV-2 infection><SARS-CoV-2 omicron><SARS-CoV-2 omicron variant><SARS-CoV-2 severity><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 exposure><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Serodiagnoses><Serological Diagnosis><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 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 exposure><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Socio-economic status><Socioeconomic Status><Symptoms><T cell response><T-Cells><T-Lymphocyte><T4 Cells><T4 Lymphocytes><Time><Transplant Recipients><Transplantation><Underrepresented Groups><Underrepresented Populations><United States><Vaccinated><Vaccination><Vaccine Design><Vaccines><Variant><Variation><Viral><Virus><Vulnerable Populations><Work><Wuhan coronavirus><adaptive immune response><adaptive immunity><adiposity><ages><antibody against COVID-19><antibody against SARS-CoV-2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody titering><antibody to COVID-19><antibody to SARS-CoV-2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><antigen-specific T cells><autoimmune condition><autoimmune disorder><autoimmunity disease><biobank><biorepository><booster dose><booster shot><booster vaccine><breakthrough infection><cell culture><cell cultures><chronic COVID><chronic COVID-19><chronic novel coronavirus disease 2019><co-morbid><co-morbidity><comorbidity><coronavirus disease 2019 antibody><coronavirus disease 2019 antigen><coronavirus disease 2019 disease severity><coronavirus disease 2019 exposure><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic consequence><coronavirus disease 2019 pandemic impact><coronavirus disease 2019 severity><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease severity><coronavirus disease-19 vaccine><coronavirus disease-19 virus><corpulence><cross reactivity><cytokine><depository><design><designing><developmental><diagnostic platform><diagnostic serology><diagnostic system><disease severity><effects following the COVID-19 pandemic><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><hCoV19><hematopoietic cell transplantation><hematopoietic cellular transplantation><hematopoietic progenitor cell transplantation><high risk><host response><immune response to vaccination><immune response to vaccines><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><immunogen><immunopathology><immunoresponse><impact of the SARS-CoV-2 pandemic><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><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><mRNA immunization><mRNA vaccination><mRNA vaccine><mRNA-based vaccine><malignancy><mortality><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><neoplasm/cancer><neutralizing antibody><new vaccines><next generation vaccines><non vaccinated><not vaccinated><novel><novel vaccines><older adult><older adulthood><omicron variant of COVID-19><omicron variant of SARS-CoV-2><outcome following vaccination><outcome following vaccine><patient population><persistent COVID-19><post COVID syndrome><post COVID-19 syndrome><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-acute phases of COVID-19><prolonged COVID-19 symptoms><public health emergency><reconstitute><reconstitution><repository><response><result following vaccination><result following vaccine><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 B.1.1.529><severe acute respiratory syndrome coronavirus 2 B.1.617.2><severe acute respiratory syndrome coronavirus 2 antibody><severe acute respiratory syndrome coronavirus 2 antigen><severe acute respiratory syndrome coronavirus 2 disease severity><severe acute respiratory syndrome coronavirus 2 severity><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><sex><social role><socio-economic position><socioeconomic position><symptomatology><thymus derived lymphocyte><transplant><transplant patient><under representation of groups><under represented groups><under represented people><under represented populations><underrepresentation of groups><underrepresented people><unvaccinated><vaccination outcome><vaccination result><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine associated immune response><vaccine boost><vaccine candidates against SARS-CoV-2><vaccine for novel coronavirus><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><vaccine outcome><vaccine result><vaccines preventing COVID><vaccines to prevent COVID><variant of interest><vulnerable group><vulnerable individual><vulnerable people>