U19AI167891

Systems Immunology Profiling of Respiratory Viral Infections in Vulnerable Populations - 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.

Benaroya Research Institute At Virginia Mason

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Seattle, Washington 981012795 United States

Single Zip Code

Human Immunology Project Consortium (U19 Clinical Trial Optional) (RFA-AI-20-079)

Amendment Since initial award the total obligations have increased 313% from $2,283,860 to $9,440,069.