Key UK research initiatives on COVID-19 vaccines
Listed below are some of the primary UK research projects studying or developing vaccines for COVID-19, including details of the specific questions they are addressing, which institutions are involved, and how they are funded.
National Core Studies: Immunity programme
The UK Government’s National Core Studies (NCS) programme is enabling the UK to use health data and research to inform both our near and long-term responses to COVID-19, as well as accelerating progress to establish a world-leading health data and research infrastructure for the future.
The National Core Studies consists of six programmes, two of which contribute directly to vaccine research:
- Epidemiology and Surveillance – collecting data to inform safe level of restrictions and protection against imminent outbreaks (led by Ian Diamond, UK National Statistician, ONS).
- Clinical Trials Infrastructure – building on established NIHR infrastructure (and equivalent in Devolved Administrations) to accelerate delivery of large scale Covid trials for drugs and vaccines. (led by Patrick Chinnery, Clinical Director, MRC and Divya Chadha Manek, Head of Business Development, Vaccines Task Force).
- Transmission and Environment (also known as PROTECT) – improving our understanding of how the virus is transmitted in different settings and environments, including in workplaces, on transport and in other public places (led by Andrew Curran, Chief Scientific Adviser, Health and Safety Executive).
- Immunity – understanding immunity against Covid to inform back-to-work policies (led by Paul Moss Professor of Haematology, University of Birmingham).
- Longitudinal Health and Wellbeing – using data from longitudinal studies to address the impact of COVID-19 and of associated viral suppression measures on health and wealth to inform mitigating strategies (led by Nishi Chaturvedi, Professor of Clinical Epidemiology, University College London).
- Data and Connectivity – making data from all studies available and accessible to inform decision makers and catalyse COVID-19 research (led by Andrew Morris Director, HDR UK).
Oxford Vaccine Trials
These trials were in part funded by UK Research and Innovation, to the sum of £65.5 million, since the pandemic began. The work that preceded the release of the Oxford/AstraZeneca vaccine actually began years before the pandemic started. In 2015, the Oxford team was funded by the UK Vaccine Network – a partnership between the Department of Health and Social Care and UKRI’s Medical Research Council and Biotechnology and Bioscience Research Council – to develop a vaccine for Middle Eastern Respiratory Syndrome (MERS), an illness caused by a different coronavirus. It was during this time that the team fine-tuned the adenovirus vaccine platform. In 2018, the vaccine entered safety trials and was shown to cause no adverse responses, whilst eliciting both cellular and antibody immune responses. The team’s research suggested that two doses would be more effective than one.
The MERS virus has a spike protein on its surface similar to the SARS-CoV-2 spike protein. This, along with the previous testing of the vaccine platform technology, meant that the Oxford team already had an adaptable vaccine that had been tested – and proved safe – in humans. Once the genomic sequence of the SARS-CoV-2 had been shared by the Chinese investigators, this could then be inserted into the adenovirus in order to produce the prototype COVID-19 vaccine that entered into human trials in April 2021.
Being able to deliver such a vaccine at pace was the product of long-term funding through UKRI over the span of more of a decade, which ensured an existing vaccine platform technology alongside optimised manufacturing methods. The Oxford/AstraZeneca vaccine development was also facilitated by a £2.6 million UKRI/NIHR Rapid Response grant in March 2020, which provided funding to conduct pre-clinical investigations and a phase I/II trial, and scale up production of the vaccine to one million doses by summer 2020.
Currently, the Oxford Vaccine Group is working on the Com-COV studies (see Current Studies). The Com-COV2 study is investigating how well people’s immune systems respond when their second ‘boost’ vaccine dose is a different type of vaccine to their first ‘prime’ dose. They are also looking at how common vaccine reactions, such as fever, are after such ‘mixed’ schedules. This is important, as being able to use different vaccines in this way creates a more flexible immunisation programme, potentially allowing more people to be immunised more quickly. This is being funded by UK Vaccine Taskforce, the National Institute of Health Research (NIHR) and the Coalition for Epidemic Preparedness Innovations (CEPI).
The UK Coronavirus Immunology Consortium (UK-CIC) is a UK-wide study launched to tackle some of the key questions about the immune system’s response to SARS-CoV-2, for example: why does it make some people sick and not others, what constitutes effective immunity, and how long might that immunity last? The immune system is extremely complex, and so to make rapid and effective progress in our knowledge, a cohesive and nationally coordinated approach is required.
This innovative project received £6.5million of funding over 12 months from UK Research and Innovation (UKRI) and the National Institute for Health Research (NIHR), which is the largest immunology grant awarded to tackle the COVID-19 pandemic. It was supported by the British Society for Immunology.
The UK-CIC was funded in a way almost unique to COVID-19 research, encouraging collaborative, team science. UK-CIC has seen 20 of the UK’s leading immunology research institutes funded as a consortium, focused around five themes:
- primary immunity
- protective immunity
- cross-reactive coronavirus immunity
- immune evasion
UK-CIC has proved highly effective and should be strongly considered as a model for future funding of research. Notable successes to date include:
- Exploring a role for interferon therapy.
- Determining the effectiveness of dexamethasone.
- Showing that extended dosing interval (12 weeks) between vaccine doses is more effective than a shorter (3 week) interval.
- Showing that there was a stronger antibody response to mRNA vaccines, e.g., Pfizer.
- Showing that there were stronger cellular immune responses to ChAdOx1 vaccines, e.g., AstraZeneca.
- Contributing to studies on COVID vaccines with immunosuppressed groups.
- Curating the largest collection of COVID-19 post-mortem tissue in the world.
- Defining the 4 main subtypes of inflammation in COVID-19.
- Finding that T cell responses are likely to overcome viral mutations.
HICC (Humoral Immune Correlates for COVID-19)
HICC is one of three UK-wide studies receiving a share of £8.4 million from UK Research and Innovation (UKRI) and the National Institute for Health Research (NIHR) to understand immune responses to SARS-CoV-2. The consortium is a collaboration led by Dr Helen Baxendale at Royal Papworth Hospital NHS Foundation Trust and Professor Wilhelm Schwaeble and Professor Jonathan Heeney at the University of Cambridge.
The research team is studying the humoral immune response (molecules, including antibodies, produced by the immune system to fight infection) by focusing on two cohorts: NHS workers (in collaboration with the SIREN study) to track immunity over 12 months, and hospitalised patients. The aim is to understand and develop highly accurate tests to identify when a person has developed a protective immune response versus a COVID-19 disease response.
PITCH (Protective Immunity from T cells to Covid-19 in Health workers)
PITCH is a national collaboration of universities aiming to understand the way the immune system responds to the COVID-19 virus in healthcare workers. The team hopes to answer important questions about how our bodies respond to infection and the immune responses they develop. In particular, they are seeking to understand the contribution of T-cells and their involvement in immunity to the virus, as well as how vaccination alters this response. PITCH is a sub-study of SIREN (see below).
SIREN (SARS-COV2 immunity and reinfection evaluation)
The aim of SIREN is to find out whether healthcare workers who have evidence of prior COVID-19 (detected by positive antibody tests) are protected from future episodes of infection, compared to those who do not have evidence of infection. Nearly 50,000 healthcare professionals enrolled in the existing SIREN study are given PCR tests every two weeks, as well as regular antibody blood tests.
In August 2021, the UK Health Security Agency (UKHSA) announced £1.5 million in funding from UKRI for SIREN, together with a number of other consortia, to lead a study to understand why some people become infected after vaccination or prior infection while others do not.
ISARIC4C (Coronavirus Clinical Characterisation Consortium)
ISARIC4C a UK-wide consortium of doctors and scientists committed to answering urgent questions about COVID-19 quickly, openly, and for the benefit of all. Having spent nine years preparing for such a major outbreak worldwide, the team deployed immediately at the start of the pandemic and has been collecting data and samples since the first cases were reported in the UK. Their work has contributed to other studies and trials of new treatments. For example, at the start of the pandemic, ISARIC4C was able to provide convalescent samples of PCR-positive hospitalised patients with COVID-19 to characterise the immunological properties of the virus, which was essential to the development of the viral vectored coronavirus vaccine developed by the Oxford COVID Vaccine Trial Group. As of August 2021, ISARIC4C had recruited 227,178 cases and have biological sampling on 2,462. ISARIC4C is funded by two major awards from UKRI and NIHR, with the immunology component being funded via UK-CIC.
The OCTAVE study is investigating the immune response mounted by immunocompromised people. Preliminary data shows that 89% of immunocompromised people generate antibodies after vaccination and that 60% of immunocompromised people generate a strong antibody response after two doses. The OCTAVE DUO study is investigating the effect of a third vaccine dose on the group with an undetectable or low vaccine response.
EAVE II tracks - in near real-time - the COVID-19 pandemic, as well as the effectiveness of the COVID-19 vaccines, across Scotland. This is done using a rich dataset of all 5.4 million people registered with a GP in Scotland, around 98% of the Scottish population. The study’s findings have been central to the Scottish and UK governments’ responses to the COVID-19 pandemic.
EAVE II is led by researchers at the University of Edinburgh, working in collaboration with the Universities of St. Andrews, Strathclyde, and Aberdeen; Public Health Scotland; and the West of Scotland Specialist Virology Centre. The study is endorsed by the Scottish Government and funded by the Medical Research Council.
UK Coronavirus Cancer Programme
The UK Coronavirus Cancer Programme (UKCCP) was established in March 2020 and is one of the longest running and most successful pandemic response programmes for cancer patients. Its mission is to safeguard, evaluate and protect cancer patients during the COVID-19 pandemic through population-scale, real-world evaluations. Its is delivered by over 250 individuals who contribute from 86 cancer centres. Its projects have demonstrated how to deliver safe cancer care during the pandemic, and have also provided scientific evidence for approaches and strategies to maximise patient safety.