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Principal Investigator: Shane P Crotty
Organization: LA JOLLA INSTITUTE FOR IMMUNOLOGY
Fiscal Year: 2024
Award: $2,595,434
Funding agency: National Institute of Allergy and Infectious Diseases
OVERALL COMPONENT SUMMARY
Our LJI CCHI was first funded in April of 2019 and has been highly impactful in human immunology research in
the past < 4 years, particularly in the areas of COVID and COVID vaccines. Crotty and Sette published the first
major paper on virus-specific T cell and antibody responses in COVID cases ( > 3,000 citations) and went on to
collaboratively publish several more of the most influential T cell, B cell, and immune memory papers on COVID
and COVID vaccines. The adaptive immune system is important for control of most viral infections. The three
fundamental components of the adaptive immune system are B cells (the source of antibodies), CD4+ T cells,
and CD8+ T cells. The armamentarium of B cells, CD4+ T cells, and CD8+ T cells has differing roles in different
viral infections, and in vaccines, and thus it has been critical to directly study adaptive immunity to SARS2
(SARS2) to understand COVID. The COVID pandemic has been a historic disaster, with over 1 million American
deaths and millions of deaths and billions of infections around the world, counterweighted by the exceptionally
efficient development of COVID vaccines which had remarkable efficacy and have saved over 15 million lives in
less than two years. In 2023 COVID remains a major American public health problem and global health problem,
with COVID being the #3 cause of death in the USA in 2022, and in the USA there were over 1.6 million confirmed
new cases of COVID in the month of January 2023 alone. Improvements in controlling COVID remain somewhat
impaired by our limited understanding of immune memory and upper airways immunity to SARS2. The
overarching focus connecting the three Projects in this LJI CCHI renewal proposal is immune memory, with
emphasis on COVID, highlighted by three overall LJI CCHI themes: (1) understanding immune memory in
humans from blood samples, rich in complexities; (2) understanding human upper airways T and B cell biology
and memory; and (3) COVID immunobiology, including breakthrough infections, differences between COVID
vaccines, and immunity relatedness to other respiratory viral infections of humans. These three themes are
explored in depth in Projects 1-3 and the Clinical Core.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><Acute><Adaptive Immune System><Address><Adenoidal structure><Adenoids><Affect><Aged 65 and Over><American><Antibodies><Antibody Response><Antigens><Area><Aspergillus><Automobile Driving><B blood cells><B cell><B cells><B pertussis infection><B-Cells><B-Lymphocytes><B-cell><B-cell receptor repertoire sequencing><B-cell receptor sequencing><B. pertussis infection><BCR repertoire sequencing><BCR seq><BCR sequencing><BCRseq><Back><Biology><Blood Sample><Blood specimen><Body Tissues><Bordetella pertussis infection><CAIV-T><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><CITE sequencing><CITE-seq><CITEseq><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 vaccine><COVID-19 virus><COVID-19 years><COVID19 virus><CV-19><Cancers><Candida><Cause of Death><Cell Body><Cells><Cellular Indexing of Transcriptomes and Epitopes by Sequencing><Cellular biology><Cessation of life><Clinical><Clonality><CoV-2><CoV2><Complement><Complement Proteins><Coronavirus Infectious Disease 2019><Data><Death><Development><Diabetes Mellitus><Disasters><Dorsum><Evolution><FluMist><Frequencies><Funding><Generations><Germinal Center><Grippe><HPV><Human><Human Papilloma Virus><Human Papillomavirus><Immune memory><Immunity><Immunization><Immunobiology><Immunologic Memory><Immunological Memory><Immunology><Immunomodulation><Immunophysiology><Impairment><Infection><Infectious Human Wart Virus><Influentials><Influenza><Life><Living Donors><Malignant Neoplasms><Malignant Tumor><Measures><Memory><Memory B Cell><Memory B-Lymphocyte><Metapneumovirus><Methodology><Modern Man><Monilia><Mucosa><Mucosal Immunity><Mucosal Tissue><Mucous Membrane><Nature><Operative Procedures><Operative Surgical Procedures><PD-1 antibody therapy><PD-1 therapy><PD1 antibody therapy><PD1 based treatment><Paper><Parainfluenza><Pertussis><Pharyngeal Tonsil><Phenotype><Play><Policies><Positive Test Result><Property><Proteome><Public Health><Publishing><RNA Seq><RNA sequencing><RNAseq><Research><Rest><Role><Route><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 pandemic><SARS-CoV-2 vaccine><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><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 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 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Shapes><Smoking><Source><Structure of germinal center of lymph node><Surface><Surgical><Surgical Interventions><Surgical Procedure><T cell response><T memory cell><T-Cells><T-Lymphocyte><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><Testing><Time><Tissues><Upper respiratory tract><Vaccinated><Vaccination><Vaccines><Variant><Variation><Viral><Viral Diseases><Viral Respiratory Tract Infection><Virus><Virus Diseases><War><Whooping Cough><Wuhan coronavirus><aPD-1 therapy><aPD-1 treatment><aPD1 therapy><aPD1 treatment><above age 65><acquired immune system><adaptive immunity><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age associated effects><age effect><age of 65 years onward><age related effects><aged 65 and greater><aged 65+><aged ≥65><aging effect><anamnestic reaction><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><breakthrough infection><cell biology><cellular indexing of transcriptomes and epitopes by single cell sequencing><co-morbid><co-morbidity><cohort><comorbidity><complementation><coronavirus disease 2019><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 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus infectious disease-19><cross reactivity><developmental><diabetes><driving><exhaustion><experience><flu virus pandemic><global health><hCoV19><human old age (65+)><immune modulation><immune regulation><immune response to vaccination><immune response to vaccines><immunogen><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><impact of age><improved><in vivo><infected with B pertussis><infected with B. pertussis><infected with Burkholderia pertussis><influence of age><influenza virus pandemic><innovate><innovation><innovative><insight><interest><malignancy><memory T lymphocyte><multi-modality><multimodality><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><nasopharyngeal swab><neoplasm/cancer><neutralizing antibody><old age><over 65 years><pandemic flu><pandemic influenza><pandemic strain of influenza><pathogen><pathogenic virus><programmed cell death protein 1 therapy><respiratory pathogen><respiratory virus><response><secondary immune response><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><single cell analysis><social role><surgery><thymus derived lymphocyte><transcriptome sequencing><transcriptomic sequencing><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 associated immune response><vaccine candidates against SARS-CoV-2><vaccine for novel coronavirus><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><vaccine response><vaccine responsiveness><vaccine-induced response><vaccines preventing COVID><vaccines to prevent COVID><viral infection><viral pathogen><viral respiratory infection><virtual><virus infection><virus pathogen><virus-induced disease><wart virus><≥65 years>