Drivers of influenza A virus transmission in humans

Emory University, Atlanta GA

Investigators

Abstract

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.