Coronavirus research in the MRC TIDU (HIU)
Researchers from across the Medical Research Council Translational Immune Discovery Unit (previously Human Immunology Unit) are working hard to understand coronavirus infection and help combat the COVID-19 pandemic. Here you can find out more about our projects.
Professor Tao Dong - Protective Immune Responses
Professor Dong’s group had long term interest in studying the antigen-specific T cells in acute and chronic virus infection, in particular their roles in protection or disease pathogenesis. She has established collaborative networks in China, especially with the two largest infectious disease hospitals in Beijing. Since the start of the pandemic, the group has been working with colleagues in Oxford and in China, testing samples taken from COVID-19 positive patients, taken at different time points in their illness, and trying to understand why some people with a COVID-19 infection are able to fight it off successfully, while others get really ill. The team believes understanding the immune response to COVID-19 is going to be key to defeating it. They recently found broad and strong SARS-CoV-2 specific immune responses in the patients recovered from COVID-19, and identified clusters of target antigens in the virus can be seen by the T cells (doi: 10.1038/s41590-020-0782-6). As a result of this work, Professor Dong’s group with other immunologists, are developing a diagnostic cocktail consisting of the T cell antigen peptides identified, which they think will be complementary to the antibody test at an early stage of infection. Other findings from her group include Longitudinal COVID-19 profiling of cytokines and chemokines with disease severity, which was published in JCI Insight early this month (10.1172/jci.insight.139834); Host genetic factor is associated with disease severity in COVID-19, published in Journal of Infectious Disease (10.1093/infdis/jiaa224).
In addition, Professor Dong agreed with Professor Cao Xuetao, as Directors of the CAMS Oxford Institute and chief scientist for the COI core support funded by CAMS Innovation fund, to prioritise 7 COVID-19 research projects earlier this year.
Professor Dong also coordinated a large donation of PPE to Oxford University and hospitals by one partner University in China, Nankai University, including 150,000 N95 and surgical masks and 20,000 nasal swab kits in early April.
Professor Alain Townsend - Neutralising Antibodies and Protein Vaccines
Professor Townsend (Radcliffe Department of Medicine) is identifying and characterising monoclonal antibodies from patients who have recovered from COVID-19 with a view to the development of future therapeutics. In the longer term, he is working with Professor Mark Howarth in the Department of Biochemistry in Oxford to make a protein aggregate vaccine based on the spike protein. Overall, this work will contribute to vaccine and therapeutic developments.
Drs Giorgio Napolitani & Mariolina Salio – COVID-19 pathogenesis, diagnostics and vaccines
To accelerate the development of diagnostics and vaccines for SARS-CoV2 and our understanding of COVID-19 pathogenesis, we need tools to define how the immune system responds to SARS-CoV2, and whether vaccines in development can induce immune responses with the potential to protect against this virus. Drs Napolitani and Salio will focus on T cells which have the capacity to kill other cells infected with viruses. They will identify which parts of the virus these T cells recognise which will help us to generate tools to understand whether patients with COVID-19 or individuals vaccinated with candidate vaccines against this disease develop SARS-CoV2 specific T cells capable of protecting against infection. In addition, these tools will also support the development of diagnostics. They are also collaborating with Dr Hashem Koohy at the MRC Human Immunology Unit to use bioinformatic approaches to predict which parts of the virus might be recognized by T cells
Prof Ling-Pei Ho – clinical trials of drug treatment and immune responses in the lungs
Prof Ling-Pei Ho leads the NIHR Translational Research Collaboration network in its efforts to accelerate novel drugs with high scientific value to treatment for COVID-10 patients. With Tracy Hussell in Manchester, the network works collaboratively identify early immune signals for severe disease. In the WIMM, she combines her group’s interest in a blood cell type (monocytes) with colleagues in the MRC Molecular Haematology Unit to understand the pathogenesis of severe disease. She has local roles in designing and coordinating clinical trials and serves on the Urgent Public Health England group to prioritise the nation’s clinical trials.
Professor Alexander Hal Drakesmith – iron biology and COVID-19
A feature of patients with severe COVID-19 infection is anaemia and changed concentrations of iron in the bloodstream. Professor Drakesmith’s laboratory is investigating whether the altered iron levels and the anaemia might cause less efficient immune responses against the virus, allowing the infection to persist. If so, therapies aimed at correcting iron imbalances might improve the outcome of infection.
Professor Graham Ogg and Professor Richard Cornall are on the University of Oxford Immunology Steering Committee to help lead wider COVID-19 immunology research and to integrate into wider university activities of vaccine development, clinical trials, epidemiology, serology, clinical studies and contact tracing. These activities include collaborations with Paul Klenerman, Gavin Screaton, Julian Knight, Andrew Pollard, Sarah Gilbert, Teresa Lambe, William James and Alex Mentzer, and many others. The work also integrates into the NHS, and national and international collaborations. Richard Cornall chairs the weekly university meeting to bring the diverse aspects together.
Associate Professor Jan Rehwinkel - Detection of SARS-CoV2 Infection by The Innate Immune System
Human cells respond to infection by SARS-CoV2, the virus that causes COVID-19, by producing immune signalling molecules called cytokines. During early infection, cytokines limit virus multiplication. However, cytokine imbalance contributes to severe COVID-19 at later stages. We investigate how cells detect that they are infected with SARS-CoV2, and how the virus counteracts this response. Identifying the cellular pathways that govern cytokine production may reveal new targets for therapeutic intervention.
Provision of platforms and expertise for wider community collaborations
The Human Immunology Unit has access to core platforms to support collaborative work, including flow cytometry, CyTOF, imaging CyTOF, super-resolution imaging, T cell bioinformatic expertise, and sequencing. With new MRC-funded equipment (Cell Sorter, 10x Chromium, BD Rhapsody, High-throughput Luminex) the Unit will be well-equipped to address major scientific questions towards diagnosis, vaccination, therapeutics and mechanisms underlying COVID-19 disease.
Richard Cornall chairs the weekly university meeting to bring the diverse aspects together