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Principal Investigator: Pandurangan Vijayanand
Organization: LA JOLLA INSTITUTE FOR IMMUNOLOGY
Fiscal Year: 2024
Award: $572,159
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
La Jolla HIPC team will focus on common pathogens causing infectious diseases of the respiratory tract.
Here in Project 3, we will determine the molecular properties of lung tissue-resident memory T cells (TRM cells)
that are specific to a wide-range of viral, bacterial and fungal pathogens. Our goal is to establish a single-cell
atlas of the transcriptome, epigenome and T cell receptor (TCR) repertoire of pathogen-reactive lung TRM cells.
In Aim 1, we will perform single-cell RNA-seq, ATAC-seq, and TCR-seq analysis of T cells isolated from lung
tissue and bronchoalveolar lavage (BAL) of 100 living donors, who undergo surgical resection for suspected
early-stage lung cancer (TARGET Lung study). We will utilize their TCR sequences to determine the pathogen-
specificity of lung TRM cells. To achieve this goal, we will generate a catalogue of experimentally-validated TCR
sequences that are specific to different pathogen epitopes and HLA-typed donors; we will achieve this goal by
stimulating PBMCs of matched donors with peptide pools targeting specific pathogens that infects the lungs such
as: viral (Influenza, respiratory syncytial virus, para influenza, meta pneumovirus, SARS-CoV-2, common cold
corona virus), bacterial (pneumococcus, pertussis, mycobacterium) and fungal (aspergillus and candida)
pathogens, and retrieve TCR sequences of responding T cells. Longitudinal assessments: To assess
persistence and plasticity of pathogen-specific lung TRM cells, in a subgroup of donors (n~25-50), we will obtain
BAL samples 1 year after initial assessments and perform single-cell analysis as above. In Aim 2, we will define
the molecular properties of human lung T cells responding to vaccination (n=100). In 100 donors (TARGET Lung
study), we will assess effects of 4 different vaccines (n=25/vaccine cohort): (i) inactivated influenza vaccine, (ii)
pneumococcal vaccine (PPSV23), (iii) SARS-CoV-2 vaccine, (iv) Pertussis vaccine (Boostrix-IPV). We will
compare the molecular features of circulating and lung T cells (TRM cells) that respond to vaccines targeting
different pathogens. In addition, we will determine if vaccine-responding T cells in the blood truly reflect TRM
responses in the lung tissue. Longitudinal assessments: We will also collect repeat blood and BAL samples,
obtained by research bronchoscopy, 12 months after vaccination. We will determine the magnitude and
phenotype of vaccine-responsive T cells in the blood and lungs to assess their persistence and plasticity. We
have extensive synergies with Project 1 and 2, especially the focus on generating immune signatures of various
respiratory pathogen-specific T cells.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><ATAC sequencing><ATAC-seq><ATACseq><Abscission><Acute Nasopharyngitis><Airway infections><Allergy><Antigenic Determinants><Aspergillus><Assay><Assay for Transposase-Accessible Chromatin using sequencing><Atlases><Automobile Driving><B pertussis infection><B. pertussis infection><B. pertussis vaccine><Basal Transcription Factor><Basal transcription factor genes><Binding Determinants><Bioassay><Biological Assay><Blood><Blood Reticuloendothelial System><Bordetella pertussis infection><Bordetella pertussis vaccine><Bronchioalveolar Lavage><Bronchoalveolar Lavage><Bronchopulmonary Lavage><Bronchoscopy><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><COVID infected patient><COVID patient><COVID positive patient><COVID-19 infected patient><COVID-19 patient><COVID-19 positive patient><COVID-19 vaccine><COVID-19 virus><COVID19 patient><COVID19 positive patient><COVID19 virus><Cancers><Candida><Catalogs><Cell Body><Cell Isolation><Cell Segregation><Cell Separation><Cell Separation Technology><Cells><Clinical><CoV-2><CoV2><Common Cold><Communicable Diseases><Coronaviridae><Coronavirus><D pneumoniae><D. pneumoniae><Diplococcus pneumoniae><Enhancers><Epitopes><Excision><Extirpation><Gene Transcription><General Transcription Factor Gene><General Transcription Factors><Genetic Transcription><Genus Mycobacterium><Goals><Grippe><Health><Human><Human Characteristics><Human Nature><Hypersensitivity><Immune><Immunes><Immunology><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Influenza><Influenza Vaccines><Link><Living Donors><Lower respiratory tract structure><Lung><Lung Lavage><Lung Parenchyma><Lung Respiratory System><Lung Tissue><MHC Receptor><Major Histocompatibility Complex Receptor><Malignant Neoplasms><Malignant Tumor><Malignant Tumor of the Lung><Malignant neoplasm of lung><Modern Man><Molecular><Monilia><Mucosa><Mucosal Tissue><Mucous Membrane><Mycobacterium><Nature><Operative Procedures><Operative Surgical Procedures><PBMC><PD-1 antibody therapy><PD-1 therapy><PD1 antibody therapy><PD1 based treatment><Peptides><Peripheral Blood Mononuclear Cell><Pertussis><Pertussis Vaccine><Phenotype><Pneumococcal vaccine><Pneumococcus><Pneumoviridae><Pneumovirinae><Pneumovirus><Property><Pulmonary Cancer><Pulmonary malignant Neoplasm><RNA Expression><Removal><Research><Respiratory Infections><Respiratory Tract Diseases><Respiratory Tract Infections><Respiratory syncytial virus><S pneumoniae><S. pneumoniae><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infected patient><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 vaccine><SARS-CoV2><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><Science><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 vaccine><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Specificity><Streptococcus pneumoniae><Streptococcus pneumoniae vaccine><Structure of parenchyma of lung><Subgroup><Surgical><Surgical Interventions><Surgical Procedure><Surgical Removal><T cell receptor repertoire sequencing><T cell receptor sequencing><T-Cell Antigen Receptors><T-Cell Receptor><T-Cells><T-Lymphocyte><T-cell receptor repertoire><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><TCR repertoire><TCR repertoire sequencing><TCR sequencing><TCR-seq><TCRseq><Tissue Sample><Transcription><Transcription Factor Proto-Oncogene><Transcription factor genes><Upper respiratory tract><Vaccinated><Vaccination><Vaccine against B. pertussis><Vaccine against Bordetella pertussis><Vaccine against pertussis><Vaccines><Viral><Viral Diseases><Virus Diseases><Whooping Cough><Wuhan coronavirus><aPD-1 therapy><aPD-1 treatment><aPD1 therapy><aPD1 treatment><anti-PD-1 therapy><anti-PD-1 treatment><anti-PD1 therapy><anti-PD1 treatment><anti-programmed cell death 1 therapy><anti-programmed cell death protein 1 therapy><anti-tumor immune response><antigen-specific T cells><assay for transposase accessible chromatin followed by sequencing><assay for transposase accessible chromatin seq><assay for transposase accessible chromatin sequencing><assay for transposase-accessible chromatin with sequencing><bacteria pathogen><bacterial pathogen><bronchopulmonary lavage therapy><cancer type><catalog><cell sorting><cellular targeting><cohort><corona virus><coronavirus disease 2019 infected patient><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19 patient><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus patient><disease severity><driving><epigenome><epigenomics><evaluate vaccines><flu><flu vaccine><flu virus vaccine><fungal pathogen><fungi pathogen><global gene expression><global transcription profile><hCoV19><infected with B pertussis><infected with B. pertussis><infected with Burkholderia pertussis><influenza virus vaccine><insight><lower respiratory tract><lung cancer><malignancy><model organism><mouse model><murine model><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><neoplasm/cancer><novel><pathogen><pathogenic bacteria><pathogenic fungus><pathogenic virus><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><programmed cell death protein 1 therapy><programs><prospective><pulmonary><recruit><resection><resident memory T cell><respiratory pathogen><response><scATAC sequencing><scATAC-seq><scRNA-seq><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><single cell ATAC-seq><single cell ATAC-sequencing><single cell Assay for Transposase Accessible Chromatin sequencing><single cell RNA-seq><single cell RNAseq><single cell analysis><single cell expression profiling><single cell sequencing assay for transposase accessible chromatin><single cell transcriptomic profiling><single-cell Assay for Transposase-Accessible Chromatin with sequencing><single-cell RNA sequencing><single-cell assay for transposase-accessible chromatin using sequencing><single-cell assay for transposase-accessible chromatin-seq><surgery><synergism><thymus derived lymphocyte><tissue resident memory T cell><transcription factor><transcriptome><transcriptomics><upper airway tract><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 against flu><vaccine against influenza><vaccine candidates against SARS-CoV-2><vaccine evaluation><vaccine for novel coronavirus><vaccine response><vaccine responsiveness><vaccine screening><vaccine testing><vaccine-induced response><vaccines preventing COVID><vaccines to prevent COVID><viral infection><viral pathogen><virus infection><virus pathogen><virus-induced disease>