Defining immune responses to emerging and re-emerging viral infections
Respiratory viruses such as influenza and SARS-CoV-2 are constant threats to global health. Drawing on their pioneering studies, cutting-edge technologies and powerful clinical cohorts, Katherine’s group has been at the forefront of global research to provide urgently needed knowledge on immune responses underlying recovery or susceptibility to severe/fatal disease from respiratory viruses, with a focus on protective killer T cells. Katherine’s group was the first in the world to publish on immune responses preceding recovery from COVID-19. Their findings provided the immunological blueprint to the global research community on immune responses in COVID-19. Their data and assays were utilised by researchers worldwide (1183 citations) and these in-depth immunological protocols developed for COVID-19 were used to evaluate COVID-19 vaccines, including the University of Queensland and Doherty Institute vaccine candidates, and COVID-19 vaccines in high-risk groups, including First Nations people, patients with cancer and autoimmune diseases. The Kedzierska Lab’s pioneering COVID-19 work was based on a decade of research on immunity to emerging and re-emerging viral infections, together with well-established ‘ready to go’ protocols for understanding immunity to newly-emerging potentially pandemic viruses, with a rapid access to diverse patient cohorts.
To identify correlates of severe and fatal respiratory virus disease in high-risk groups
Enhanced susceptibility and exacerbated disease severity to respiratory viruses such as influenza and SARS-CoV-2 can reflect over-activation of the innate immune system, impaired humoral and cellular immunity, and can be influenced by host genetic factors (HLA or IFITM3). Understanding the immune perturbations that lead to severe disease in high-risk groups will provide insight into how immune interventions might minimise the incidence of severe disease. Katherine’s group studies the contributions of virological, immunological, clinical, molecular and host factors to susceptibility, clinical severity and outcome for different high-risk groups: (i) young children and the elderly (with Professor Katie Flanagan from Launceston General Hospital and Dr Jane Crowe from Deepdene Surgery); (ii) Australian First Nations people (with Professor Jane Davies from Menzies and Professor Adrian Miller from Central Queensland University); (iii) pregnant women (with Susan Walker from the Mercy Hospital/UoM); and (iv) high-risk groups hospitalised through FluCAN (with Professor Allen Cheng and Associate Professor Tom Kotsimbos from the Alfred Hospital) and Shanghai Public Clinical Hospital at Fudan University in China (with Professor Xu). As part of their multidisciplinary approach, the Kedzierska Lab uses murine models to further define mechanisms and biomarkers underpinning severe and fatal disease from viral infections. Furthermore, their work also examines the efficacy of virus-specific immune responses to vaccination in high-risk groups, including Australian First Nations people and patients with cancer and autoimmune diseases (with Professor Benjamin Teh from The Peter MacCallum Cancer Centre). These finding provide key information for vaccine development and delivery to protect these high-risk groups.
To define ‘universal’ influenza-specific CD8+ T-cell responses across different human leukocyte antigens (HLAs)
Although CD8+ T cells confer broadly cross-reactive or ‘universal’ immunity to distinct influenza viruses and can limit influenza-induced mortality, the overall efficacy of human influenza A virus-specific CD8+ T cells directed at any conserved and/or variable epitopes remains unclear. Here, Katherine’s group aims to (i) understand influenza-specific CD8+ T cell immunity across different HLAs; (ii) determine the efficacy of immunodominant CD8+ T cell responses in humans; (iii) evaluate the conservation of immunogenic epitopes in birds, pigs and humans through analysis of viral evolutionary history; and (iv) understand immunity to clinically important but understudied influenza B viruses. This work has key implications for the design of universal broadly protective influenza vaccines not requiring annual reformulation. As the Kedzierska Lab have shown that current inactivated influenza vaccines do not induce CD8+ T cell immunity, their research also focuses on how to elicit protective CD8+ T cell immunity by vaccination.
To unravel mechanisms underlying the early generation of human CD8+ T cell memory
Though immunological memory is of pivotal importance for vaccine development and immunotherapy, the molecular and differentiation pathways central to the generation of (particularly) human CD8+ T cell memory are poorly understood. Here, Katherine’s group aims to establish the key factors driving the early establishment of influenza-specific T cell memory. As memory is crucial for protection against recurrent infections, this work will provide novel insights into the generation and efficacy of human T cell memory populations and inform effective immunotherapy strategies.
The impact of co-infection on immune responses to influenza
Infectious diseases are often studied in isolation, by measuring parameters in an individual with a known infection or in an experimentally infected animal. However, the reality is that people can have more than one infection, perhaps in sequence or concurrently, and that each may affect the other, often having a negative effect on human health. The Kedzierska Lab is interested in understanding how co-infection of influenza with other viruses can affect disease outcome. Arboviruses (vector-borne RNA viruses transmitted by arthropods such as ticks or mosquitos), have been responsible for epidemics with a high burden of neurological disease (e.g. Japanese encephalitis virus (JEV), West Nile, tickborne, encephalitis and Zika viruses). Considering that many neurotropic arboviral infections are asymptomatic, but the virus appears to persist in the brain for the life of the host, there remain many key questions about the effect that these virus infections have on the development of the immune response to a second virus infection and the potential to exacerbate disease severity. Work in the Kedzierska Lab dissects the immunological, virological and immunopathological changes that occur during co-infection with two viral pathogens.
Professor Katherine Kedzierska
+61 3 8344 7962 | firstname.lastname@example.org
- Laboratory Head
- Immunology, Viral Infectious Diseases, Influenza
- Discovery Research, Global Health, Indigenous Health, Clinical and health systems research
- The University of Melbourne, Department of Microbiology and Immunology (DMI)
- Lab Group(s):
- Kedzierska Group
Professor Katherine Kedzierska is Head of the Human T cell Laboratory in the Department of Microbiology and Immunology at the Doherty Institute. Katherine also holds the positions of Deputy Head of the Department of Microbiology and Immunology, Chair of the Departmental Graduate Research Committee and Visiting Professor at Hokkaido University (Sapporo, Japan). Katherine is a NHMRC Investigator Fellow, Dame Kate Campbell Fellow and Fellow of the Australian Academy of Health and Medical Sciences. Katherine received her PhD from Monash University in 2002, studying immunity to HIV infection with Professor Suzanne Crowe at the Burnet Institute. Katherine undertook her postdoctoral training as a NHMRC Peter Doherty Fellow at The University of Melbourne with Nobel Laureate Professor Peter Doherty before establishing her independent research group in the Department of Microbiology and Immunology in 2012.