P01AI186819

Drivers of influenza A virus transmission in humans - Summary - Overall transmission of respiratory infection in the context of both seasonal epidemics and infrequent pandemics leads to widespread health and economic disruptions.

While strategies developed to limit transmission could be very impactful, their evidence-based design is hampered by gaps in understanding of the fundamental biological and physical processes that underlie transmission.

Our multidisciplinary team will address these gaps through a well-integrated program that will examine influenza A virus (IAV) in a controlled human infection model (CHIM).

Through three program-wide specific aims we will pursue hypotheses related to both biological and physical drivers of transmission.

Aim 1 will seek to define the dynamics of viral load, immunological responses and infectious aerosol production in humans infected with seasonal IAV.

Owing to the well-defined time of infection and opportunity for frequent longitudinal sampling, the CHIM system is uniquely suited to obtain a high-resolution picture of infection dynamics.

These features of our study design will be leveraged to document the dynamics within each infected individual of viral amplification, innate responses, adaptive responses, and infectious aerosol production.

Emphasis will be placed on capturing heterogeneity both across individuals and across anatomical sites within an individual.

Aim 2 will examine the role of aerosols in mediating IAV infection and onward transmission.

While we expect to obtain insight into multiple potential modes of transmission, two aspects of our program will focus on the spread of infection through the air: a subset of participants will be exposed to aerosolized IAV and the respiratory aerosols generated by all participants will be evaluated.

These aspects of our approach will reveal the infectious potential of virus-laden aerosols and the quantity and characteristics of such aerosols produced by infected human hosts.

Aim 3 will investigate the complex relationships between host responses, viral replication, and expulsion of infectious virus into the environment.

Through the collection of diverse samples and datasets from each study participant, and integration of the information obtained through statistical and mechanistic modeling, we will seek to define the drivers of specific infection outcomes, with primary emphasis on susceptibility to and potential for transmission through expulsion of infectious virus into the air.

The experimental data, computational models and conceptual understanding attained through this research are expected to open new lines of inquiry and to directly enable an evidence-based transformation in public health strategies and biomedical interventions to control influenza.

Emory University

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]

Atlanta, Georgia 30322 United States

Single Zip Code

NIAID Investigator Initiated Program Project Applications (P01 Clinical Trial Not Allowed) (PAR-22-225)

Amendment Since initial award the total obligations have increased 99% from $2,074,701 to $4,135,277.