Clinical Core: Drivers of influenza A virus transmission in humans

SUMMARY - Clinical Core The most recent pandemic highlighted enormous deficiencies in our understanding of the transmission of respiratory viruses. Research on transmission dynamics is vital for global public health as it is foundational for the development of effective prevention, control, and response strategies. We propose the use of a controlled human infection model (CHIM) for influenza as a framework to explore the virological, immunological, behavioral and environmental drivers of transmission. The Hope Clinic of the Emory Vaccine Center is ideally positioned to contribute as the Clinical Core to the "Drivers of influenza A virus transmission in humans" P01 project. We have established an influenza CHIM at Emory University with 25 participants enrolled to date. Eighteen participants have been safely inoculated intranasally with influenza A/Perth/16/2009 virus (H3N2) with an attack rate of 83%. The Clinical Core will support the scientific agenda of the P01 by providing samples and data to Project 1, Project 2 and the Modeling Core from the separately funded CHIM trial. This trial will enroll a total of 75 participants and expose each to influenza through conventional intranasal inoculation, aerosolization, or extended interaction at close range with infected individuals. Data from the trial that we will provide to the P01 team include demographic and pertinent baseline medical information as well as clinical assessments and testing relevant to influenza illness. Through the P01-funded clinical study, which is ancillary to the trial, the Clinical Core will conduct baseline and longitudinal post-challenge sampling of mucosal sites and collection of blood. These samples will supply invaluable materials to the P01 Projects for virological and immunological analyses. In addition, collection of bone marrow at baseline from a subset of 10 individuals will allow investigation of the establishment of long-lived immune memory following infection. The Clinical Core includes an experienced and well-structured Clinical Research Site, the Hope Clinic of the Emory Vaccine Center, which has a dedicated research space, experienced personnel, and established processes for running successful clinical studies. The Clinical Core is led by Dr. Rouphael who is the current PI of the influenza CHIM at Emory and the Executive Director of the Hope Clinic. She has extensive experience in CHIM, having led trials enrolling close to 100 participants in respiratory and enteric challenges. As the Clinical Core for this P01 Program, we will build on our record of outstanding accomplishment and advance the NIAID mission in understanding transmission of respiratory pathogens.