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Principal Investigator: Alessandro Sette
Organization: LA JOLLA INSTITUTE FOR IMMUNOLOGY
Fiscal Year: 2023
Award: $2,391,540
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary – Overall
The La Jolla HIPC team will focus on pathogens causing infectious diseases of the upper and lower
respiratory tract that lead to substantial mortality and morbidity. Our approach is unique and innovative, as it
focuses on defining immune signatures (IMS) of antigen-specific CD4 and CD8 T cells generated in response to
natural infection with important respiratory pathogens such as SARS-CoV-2, Common Cold Coronaviruses
(CCC), influenza, Respiratory Syncytial Virus (RSV) and Mycobacterium tuberculosis (Mtb). Likewise, our
Program will investigate IMS of antigen-specific T cells generated following vaccination against a diverse array
of pathogens in different platforms like attenuated pathogens (BCG, yellow fever (YF)), purified proteins (acellular
Bordetella pertussis (PT) vaccines), viral vectors (J&J, SARS-CoV-2) and mRNA (Moderna and Pfizer).
In Project 1, we will perform longitudinal analysis to determine persistence and plasticity of antigen-specific
T cell responses following natural SARS-CoV-2 infection and vaccination. We will study T cell responses specific
to SARS-CoV-2 following vaccination with different vaccine platforms in previously-unvaccinated donors, and in
a longitudinal cohort of vaccinated individuals previously naturally-infected with SARS-CoV-2. In parallel studies,
we will analyze T cell responses to SARS-CoV-2 in naturally-infected unvaccinated donors. We will also analyze
T cell responses in two previously-enrolled cohorts who received YF and PT vaccinations; in both cohorts the
natural evolution and persistence of T cell responses to CCC viruses will be investigated.
In Project 2, we will perform longitudinal analysis of the IMS of Mtb-specific T cells. Here, we will build on
our progress made during the previous HIPC funding period to characterize the IMS associated with latent and
active TB disease as well as BCG vaccination. Specifically, we will characterize the longitudinal IMS of both
active and latent TB during treatment. In parallel, we will characterize the longitudinal IMS of adults
(re)vaccinated with BCG, and characterize the IMS of Mtb-specific T cells in the lung.
In Project 3, we will determine the molecular properties of pathogen-specific lung tissue-resident memory T
cells (TRM). Our goal is to establish a single-cell atlas of the transcriptome, epigenome, and T cell receptor (TCR)
of antigen-specific lung TRM targeting common pathogens that infects the lungs such as: viral (influenza, RSV,
para influenza, meta pneumovirus, SARS-CoV-2, CCC), bacterial (pneumococcus, PT, Mtb) and fungal
pathogens. The longitudinal study design will enable assessment of plasticity and persistence of lung TRM cells
following natural infection and vaccination. The synergy between Projects will allow the generation of cross-
comparable large-scale single-cell T cell signatures for respiratory pathogens/vaccines.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><ATAC sequencing><ATAC-seq><ATACseq><Acute Nasopharyngitis><Address><Adult><Adult Human><Airway infections><Antigenic Determinants><Antigens><Atlases><Attenuated><B pertussis><B pertussis infection><B. pertussis><B. pertussis infection><BCG immunization><BCG vaccination><BCG-vaccinated><Bacille Calmette-Guerin vaccinated><Bacille Calmette-Guerin vaccination><Bacillus Calmette-Guerin vaccination><Bacillus Calmette-Guérin vaccination><Bacteria><Binding Determinants><Blood><Blood Reticuloendothelial System><Body Tissues><Bordetella pertussis><Bordetella pertussis infection><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><COVID-19 infection><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><Cell Body><Cells><Cellular Assay><Clinical><CoV-2><CoV2><Common Cold><Communicable Diseases><Communication><Coronaviridae><Coronavirus><D pneumoniae><D. pneumoniae><Diplococcus pneumoniae><Disease><Disorder><Enrollment><Ensure><Epitopes><Evolution><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Funding><Generations><Goals><Grippe><H Pertussis><H. Pertussis><Haemophilus pertussis><Immune><Immune response><Immunes><Immunological response><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Influenza><LYT3><Long-term cohort><Longitudinal Studies><Longitudinal cohort><Longterm cohort><Lower respiratory tract structure><Lung><Lung Parenchyma><Lung Respiratory System><Lung Tissue><M tb><M tuberculosis><M. tb><M. tuberculosis><MHC Receptor><Major Histocompatibility Complex Receptor><Molecular><Morbidity><Morbidity - disease rate><Mycobacterium tuberculosis><NIAID><National Institute of Allergy and Infectious Disease><Pertussis><Pertussis Vaccine><Phenotype><Play><Pneumococcus><Pneumoviridae><Pneumovirinae><Pneumovirus><Property><Recurrence><Recurrent><Research Design><Research Resources><Resources><Respiratory Infections><Respiratory Tract Infections><Respiratory syncytial virus><Risk><Role><S pneumoniae><S. pneumoniae><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Services><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-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 infection><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Sorting><Streptococcus pneumoniae><Structure of parenchyma of lung><Study Type><Systems Biology><T cell response><T memory cell><T-Cell Antigen Receptors><T-Cell Receptor><T-Cell Subsets><T-Cells><T-Lymphocyte><T-Lymphocyte Subsets><T-cell receptor repertoire><T8 Cells><T8 Lymphocytes><TCR repertoire><Technology><Time><Tissues><Upper respiratory tract><Vaccinated><Vaccination><Vaccinee><Vaccines><Viral><Viral Vector><Virus><Whooping Cough><Wuhan coronavirus><Yellow Fever><adaptive immunity><adulthood><analyzing longitudinal><antigen-specific T cells><attenuate><attenuates><biomarker array><biomarker panel><burden of disease><burden of illness><cell assay><cohort><corona virus><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19 virus><cost effective><current pandemic><data management><design><designing><disease burden><disease severity><enroll><epigenome><flow cytophotometry><fungal pathogen><fungi pathogen><global gene expression><global transcription profile><hCoV19><host response><immune system response><immunogen><immunoresponse><infected with B pertussis><infected with B. pertussis><infected with Burkholderia pertussis><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><innovate><innovation><innovative><long-term study><longitudinal analysis><longitudinal outcome studies><longterm study><lower respiratory tract><marker panel><memory T lymphocyte><mortality><mtb><nCoV2><non vaccinated><not vaccinated><pathogen><pathogenic fungus><present pandemic><programs><protein purification><pulmonary><resident memory T cell><respiratory pathogen><response><social role><study design><success><synergism><thymus derived lymphocyte><tissue resident memory T cell><transcriptome><transcriptomics><unvaccinated><upper airway tract><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccine platform><years of life lost to disability><years of life lost to disease>