The human upper airway mucosa is the portal of entry and site of first replication for respiratory viruses. The immune response in this compartment plays a correspondingly key role in determining whether a virus is contained and eliminated, or able to enter, replicate, and initiate disease. Despite this importance, the mucosal immune events associated with protection and disease following exposure to respiratory viruses are understudied relative to responses in peripheral blood. My research seeks to identify protective and harmful features of mucosal immunity in humans, spanning studies of natural infections and controlled human infection models (CHIMs) with viruses and mucosal vaccines. Experimental infection studies (including RSV and SARS-CoV-2) and mucosal vaccine challenge studies (including live-attenuated influenza vaccine) have demonstrated the compartmentalisation of antibody responses between the airway mucosa and peripheral blood. These studies have additionally demonstrated early immune signatures associated with these different infection and humoral immune outcomes. Recent works have greatly expanded the ability to perform functional assessments of mucosal antibodies, including measures of pathogen neutralisation and Fc-dependent effector functions, features that are critical to immunity. By using coordinated sampling techniques and assays across natural and experimental infection studies we can begin to understand the relative contributions of different arms and compartments of immunity towards protection from severe respiratory viral infections.
Ryan Thwaites is a Lecturer in Respiratory Immunology within the National Heart and Lung Institute (NHLI), Imperial College London. Ryan Thwaites' postdoctoral research focused on the immune system of the human respiratory tract, incorporating studies of natural viral infections and 'challenge' studies in healthy adults. These challenge studies included non-infectious human models of innate immune activation (such as Toll-like receptor agonists), allergens and experimental human infection models with respiratory viruses such as Respiratory Syncytial Virus (RSV) and SARS-CoV-2. This postdoctoral work challenged the existing dogmas of viral disease severity in children, developed the minimally-invasive endophenotyping of chronic respiratory diseases, and identified the role of neutrophils in governing susceptibility to respiratory viral infections. During the COVID-19 pandemic Dr Thwaites worked within the ISARIC4C consortium to profile the immunopathogenic response to SARS-CoV-2 infection in cases of severe disease, before establishing his independent research group at the NHLI in 2021. These studies continued into monitoring the nature and longevity of immunity to SARS-CoV-2 after natural infection and vaccination. These studies sought to identify the elements of the immune response to infection that contributed to disease severity, versus those that contribute to clearing infection. The Thwaites lab group continues to study the immune response to respiratory viral infections, with particular interests in the drivers of disease severity and the factors governing susceptibility to viral infections.
Begrüßung: Professor Dr. Thomas Klinger
Moderation: Dr. Björn Corleis und Professorin Dr. Anca Dorhoi