The UK Coronavirus Immunology Consortium (UK-CIC) has achieved much in the 12 months since its launch. In this article, we review what UK-CIC researchers have achieved by working in collaboration, and the legacy they hope to leave behind.
From early in the pandemic, it became clear that studying the immunology of SARS-CoV-2, the virus that causes COVID-19, would be one of the keys to bringing it under control. Learning more about how the virus interacts with our immune system had great potential for delivering real benefits to patients and public health, helping us understand how people become unwell, why some suffer more severe symptoms than others, and what immunity might look like.
A challenge of this scale required an innovative approach to tackle these unknowns at pace, and the UK – being home to many of the world’s leading immunologists – was well-placed to take on the challenge. Collaborative science has always been a key part of academic research, but UK-CIC saw 20 research centres, with their immunologists and unique expertise, brought together in a way never seen before.
Collaboration is key
The concept of a national consortium on the immunology of COVID-19 came about in June 2020. Not long before, a paper identifying the immunology research priorities for COVID-19 was produced by the British Society for Immunology and the Academy of Medical Sciences. These priorities were adopted to become UK-CIC’s research themes. Its members would set out to understand the features of immunity in an initial infection with SARS-CoV-2, what makes some people more susceptible to severe disease, and whether immunity to other seasonal coronaviruses offered individuals any protection from SARS-CoV-2.
Collaborative science has always been a key part of academic research, but UK-CIC saw 20 research centres, with their immunologists and unique expertise, brought together in a way never seen before.
Theme 1 – primary immunity
The first research theme of UK-CIC, which focused on acute infection, sought to understand the initial immune response to SARS-CoV-2 and its relation to severe disease. Professor Tracy Hussell from The University of Manchester led the theme in close collaboration with colleagues at a number of centres around the UK including the Universities of Birmingham, Cardiff, Dundee, Edinburgh, King’s, Newcastle, Oxford, Sheffield, and Wellcome Sanger Institute.
Researchers found that early T cell responses may be helpful in preventing serious infection with SARS-CoV-2, and may underlie the efficacy of vaccines against severe COVID-19. They also found that inflammation is present very early in those who go on to experience more severe symptoms, suggesting it may be possible to screen for this inflammation to intervene when needed at an earlier stage. Related to this, many cytokines appeared to be present in greater numbers in acute disease.
Theme 2 – protective immunity
Led by Professor Paul Klenerman, University of Oxford, UK-CIC’s second theme sought to understand the specificity of the cellular response to SARS-CoV-2, and the efficacy of the immune response following prior exposure to the virus. This theme worked closely with the Protective Immunity from T Cells in Healthcare workers (PITCH) study which involves the Universities of Oxford, Liverpool, Sheffield, Newcastle and Birmingham. They also collaborated with two well-established cohort studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford.
This theme has made significant contributions to vaccine studies, having released a number of influential papers exploring the longevity and strength of the immune response to SARS-CoV-2 at several timepoints after vaccination, both in working-age and older cohorts. UKCIC research has shown that extended intervals between vaccines may be more immunogenic than a shorter interval, that mRNA COVID-19 vaccines may produce greater antibody responses in the weeks after vaccination, but that the Oxford/ AstraZeneca (ChAdOx1) COVID-19 vaccine may promote stronger cellular responses. Collaborations within UK-CIC have also studied the strength of the immune response generated in children, the presence of autoantibodies following natural infection, and the response in immune-suppressed groups.
Throughout the last 12 months, UK-CIC is pleased to have closely collaborated with the ISARIC4C study, which began collecting data and samples shortly after the very first cases of COVID-19 were reported in the UK. The data they have shared with UK-CIC collaborators have been an invaluable part of its success.
ISARIC4C’s involvement in UK-CIC is led by Professor Peter Openshaw (Imperial College London). It has made significant strides in our understanding of the virus, such as the durability of immunity to SARS-CoV-2 and how the inflammatory profile of the immune response changes with disease severity, including the identification of markers of severe disease specific to COVID-19.
Theme 3 – immunopathology
In their efforts to understand the immune response to SARS-CoV-2 on a molecular and cellular level, UK-CIC researchers have curated what is likely to be the largest collection of post-mortem tissue from COVID-19 patients in the world. Led by Professor Paul Kaye, University of York, Theme 3 has brought together researchers from universities including Cardiff, Newcastle, Sheffield, York, and the Wellcome Sanger Institute.
They have been able to define four main subtypes of inflammation, which will aid in specifying the ways in which COVID-19 damages the body, and demonstrated that complement activation plays an important role in this.
Theme 4 – cross-reactive coronavirus immunity
Led by Professor Mala Maini, University College London, and sub-led by Dr Thushan de Silva, University of Sheffield, UK-CIC researchers sought to understand if immunity to other coronaviruses, such as those that circulate seasonally, could confer any immunity to SARS-CoV-2. It looks like this may be the case.
Firstly, researchers found T cells that cross-react with both common cold viruses and SARS-CoV-2 in some people tested, and they believe this may contribute to clinical protection. Interestingly, some people were found to have cellular responses to the virus without developing an antibody response. Further results also suggested that T cell responses are likely to be able to overcome the mutations seen in some variants of SARS-CoV-2.
Theme 5 – immune evasion
This team of researchers from the Universities of Cambridge, Cardiff and Glasgow, led by Professor Paul Lehner, University of Cambridge, has been working to understand how the virus ‘hides’ from the immune system, and what can be done to overcome this. Findings from UK-CIC research suggests that SARS-CoV-2 does try to evade recognition by immune cells. Other interesting work has suggested genetic differences in how the immune system is able to control infection, which may explain differences in mortality rates in different populations.
Above all else, the success of UK-CIC has stemmed from its collaborative nature. By joining researchers together against a shared target, and removing the need to compete for funding between groups, UK-CIC researchers have been able to work to their strengths and focus on using the expertise of each group to their advantage. The sharing of samples and data across groups has been a cornerstone of the success of UK-CIC, with this having led to new insights and pools of data that others will benefit from in future. From a less results-driven perspective, many of the researchers have enjoyed being brought together in a unified effort during a time that has otherwise been difficult and isolating.
Many researchers are now keen to explore how to carry forward this model of working for scientific challenges of the future.
Patient and public involvement
A unique aspect of UK-CIC has been its inclusion of a Patient and Public Involvement (PPI) panel from the day of its launch. A new experience for many of our researchers, this provided a valuable challenge to the questions underpinning their work and the impact it may have on the public or health policy. The UK-CIC PPI panel is an example of the way the public and scientists can work together throughout the research process, with their perspectives considered at each stage rather than once results are finalised.
The COVID-19 pandemic has certainly created an unusual opportunity to do science in a new way, and UK-CIC is a testament to the potential of a truly team science approach. Many researchers are now keen to explore how to carry forward this model of working for scientific challenges of the future. Some are in discussion to set up formal collaborations between centres; others continue to expand on the work achieved over the last year; and many have a new appreciation for the benefits gained by PPI and will take this forward into their future work. We have learned so much from this unprecedented project, and must work hard to take lessons learned forward into the future of immunology research.