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Principal Investigator: Matthew C. Altman
Organization: BENAROYA RESEARCH INST AT VIRGINIA MASON
Fiscal Year: 2024
Award: $2,283,860
Funding agency: National Institute of Allergy and Infectious Diseases
SUMMARY/ABSTRACT – OVERALL
Acute respiratory viral infections (ARVI) are the most frequently occurring global illness producing significant
morbidity and mortality, particularly in vulnerable populations. Children suffer higher frequencies of ARVI and
often experience re-infections. Common chronic diseases of childhood, most notably asthma but also allergies
(atopy) and obesity, can predispose to increased severity of ARVI. Similarly, adults with chronic inflammatory
diseases or on immunosuppression suffer significant consequences from ARVI. Adults with rheumatoid arthritis
(RA) have an increased risk for infection and respiratory mucosal inflammation may contribute to autoimmune
disease severity. The goal of this research program is to understand the molecular and cellular immune
signatures of the vulnerable host response to ARVI to identify novel therapies and individuals at risk for clinical
complications. The program includes a detailed systems immunology assessment of acute and long-term
airway and adaptive systemic immune responses to naturally occurring ARVI. The first project will identify how
asthma, atopy, and obesity lead to maladaptive immune responses to ARVI in pediatric subjects. The second
project will examine host response to ARVI in adults with RA. RA is a disease provoked by environmental
stimuli like respiratory infections and RA patients have baseline immune differences. These projects are
complementary and synergistic by utilizing similar sample types and timing of sample collection, and common
clinical endpoints. The individual projects benefit from shared multi-omics approaches through a Genomics
Core for the sample processing and generation of airway host transcriptome, proteome, epithelial methylation,
and viral quantity and expression data, along with host genetics. There is also a shared Adaptive Phenotyping
Core for the generation of high dimensional cytometry data to broadly characterize immune cell phenotypes
and for detailed identification of antigen-specific cells. This will allow for direct comparisons to be made
between the adult and pediatric cohorts to identify common and divergent responses to ARVI. In the Overall,
the first Specific Aim is to determine similar and divergent host responses to ARVI considering the pediatric
allergy/asthma (Project 1) and adult RA (Project 2) cohorts. The second Specific Aim is to consider these host
responses in the context of other large publicly-funded studies of viral infection through meta-analyses. The
final Specific Aim will be to develop predictive spatiotemporal models of how mucosal and systemic immune
responses to ARVI influence clinical outcomes. Our research program will produce novel mechanistic insights
into the diversity and commonality of human immune responses to acute respiratory viruses and use cutting-
edge methods to identify potential therapies.
Terms: <0-11 years old><21+ years old><Acceleration><Acute><Adenoviridae><Adenoviruses><Adult><Adult Human><Affect><Age><Airway infections><Airway mucosa><Allergy><Antibodies><Antigens><Assay><Asthma><Atlases><Atopic Allergy><Atrophic Arthritis><Autoimmune Diseases><Bioassay><Biological Assay><Biology><Blood><Blood Reticuloendothelial System><Blood Sample><Blood specimen><Bronchial Asthma><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 immune response><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Causality><Cell Body><Cells><Characteristics><Child><Child Youth><Childhood><Children (0-21)><Chronic><Chronic Disease><Chronic Illness><Clinical><Coronaviridae><Coronavirus><Cytometry><Data><Data Analyses><Data Analysis><Disease><Disorder><Economics><Epidemic><Epithelium><Ethnic Origin><Ethnicity><Etiology><Family><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Frequencies><Funding><Future><Generations><Genetic><Genomics><Goals><Human><Hypersensitivity><Immune><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune response><Immunes><Immunodeficiency and Immunosuppression Disorders><Immunologic Diseases><Immunologic Subtyping><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Immunological response><Immunology><Immunophenotyping><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Individual><Infection><Inflammatory><Influenza Virus><Intervention><Intervention Strategies><Kinetics><Lead><Math Models><Measurement><Medical><Meta-Analysis><Metapneumovirus><Methods><Methylation><Modeling><Modern Man><Molecular><Morbidity><Morbidity - disease rate><Mucosa><Mucosal Inflammation><Mucosal Tissue><Mucositis><Mucous Membrane><Multiomic Data><NIH><National Institutes of Health><Obesity><Outcome><Pathogenesis><Patients><Pb element><Pediatric cohort><Persons><Phenotype><Proteome><Pulmonary Body System><Pulmonary Organ System><Race><Races><Research><Respiratory Infections><Respiratory Mucosa><Respiratory System><Respiratory Tract Infections><Respiratory Tracts><Respiratory syncytial virus><Respiratory tract structure><Rheumatoid Arthritis><Rhinovirus><Risk><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 immune response><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Sampling><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 immune response><Severe acute respiratory syndrome coronavirus 2 pandemic><Severities><Severity of illness><Socio-economic status><Socioeconomic Status><Stimulus><System><Systems Biology><Therapeutic><Transmission><United States National Institutes of Health><Vaccines><Viral><Viral Diseases><Viral Respiratory Tract Infection><Virus><Virus Diseases><Vulnerable Populations><adiposity><adulthood><ages><atopic triad><atopy><autoimmune condition><autoimmune disorder><autoimmunity disease><benefit sharing><causation><chronic disorder><chronic inflammatory disease><clinical risk><co-morbid><co-morbidity><cohort><comorbidity><corona virus><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 immune response><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><corpulence><data integration><data interpretation><disease causation><disease severity><economic><experience><flow cytophotometry><global gene expression><global transcription profile><heavy metal Pb><heavy metal lead><high dimensional data><high dimensionality><host response><human disease><immune suppression><immune suppressive activity><immune suppressive function><immune system response><immunogen><immunophenotype><immunoresponse><immunosuppressive activity><immunosuppressive function><immunosuppressive response><in silico><infection risk><influenzavirus><insight><interventional strategy><kids><mathematic model><mathematical model><mathematical modeling><methylome><mortality><multidimensional data><multidimensional datasets><multiomics><multiple omic data><multiple omics><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><panomics><parainfluenza virus><pathogen><pediatric><predict clinical outcome><programs><proteogenomics><racial><racial background><racial origin><respiratory infection virus><respiratory virus><response><rheumatic arthritis><sample collection><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><socio-economic position><socioeconomic position><spatiotemporal><specimen collection><therapeutically effective><transcriptome><transmission process><treatment strategy><viral infection><viral respiratory infection><virus host interaction><virus infection><virus-induced disease><vulnerable group><vulnerable individual><vulnerable people><youngster>