Project Summary/Abstract – Overall Component We propose multidisciplinary studies to comprehensively evaluate the roles of contact, fomite, sprayborne, and aerosol transmission and how they interact with ventilation to facilitate human-to-human influenza transmission using a suite of innovative technologies for improved sampling, fractionation, culture, and characterization of influenza virus aerosols. These studies leverage our highly diverse team of experts in bioengineering, aerosol science, human challenge and clinical trials, influenza virology and immunology, infectious diseases epidemiology, aerobiology, and computational fluid dynamics. The proposal is organized around two research projects and three cores. In Research Project 1, “Evaluating Modes of Influenza Transmission using a Randomized Controlled Trial (EMIT-2-RCT)” we will study the impact of two interventions a) ventilation and air sanitation and b) hand hygiene and face shields on transmission of circulating seasonal influenza from naturally infected cases to serologically susceptible volunteers. We will use the RCT to test hypotheses that aerosol transmission is the dominant mode, is associated with greater frequency of fever and systemic symptoms in secondary cases, and that in the absence of hemagglutination inhibiting antibodies, antibodies against other targets will strongly correlate with protection from infection and disease. In Research Project 2, “Developing and Applying Analytical Models of Influenza Transmission” we will use computational fluid dynamics and novel new aerosol measurements to a) design interventions and sampling strategies for the RCT enabling us to distinguish short- and long-range aerosol transmission from sprayborne transmission, b) define the Wells-Riley aerosol quantum of infection in terms of measurable quantities and assess risk at the recipient breathing zone level in both well-mixed and non-well-mixed indoor air conditions, and c) extend our models to household and animal studies and create practical analytical tools for public health scientists to collect data and assess risk in the field. The Research Projects will be enabled by an Advanced Bioaerosol Technology Core (ABTC) that will develop new viral aerosol sampling and culture systems and methods for both ambient and exhaled breath sampling that will validate the RCT design and provide critical inputs to the analytical models. A Clinical and Biostatistics Core (CBC) will provide the clinical infrastructure to perform the complex quarantine studies. The Administrative Core will manage these tightly integrated components to mold transdisciplinary insights into the dynamics and drivers of influenza transmission between humans.

Project Narrative – Overall Component Influenza is a major problem worldwide, and despite decades of research, many questions remain about the factors that affect transmission, particularly how various routes of infection contribute to transmission and disease severity. This U19 Project addresses a critical need to improve the understanding of influenza transmission in humans. To this end, our consortium of world-renowned virologists, immunologists, epidemiologists, aerosol scientists, computational fluid dynamic modelers, aerobiologists, and engineers is developing and applying state-of-the-art methods to examine transmission including the use of an experimental human transmission study and analytical models of bioaerosols.