University of Birmingham in COVID-19 booster vaccines clinical trial
Six COVID-19 vaccines are safe and boost immunity for people who have had two doses of Pfizer/BioNTech or Oxford/AstraZeneca, show results from a UK-wide trial carried out in collaboration with the University of Birmingham.
The latest results from the world-first study COV-BOOST are published in The Lancet and have been key in shaping the UK booster programme, providing vital evidence for global vaccination efforts. The trial investigated the safety, side-effects of, and immune response to, seven vaccines when used as a third booster jab.
Trial participants received one of these boosters 10-12 weeks after their initial two-dose vaccination with either Oxford/AstraZeneca or Pfizer/BioNTech vaccines. A control group was given a meningitis vaccine to account for reactions not specific to the COVID-19 jabs.1
The seven vaccines trialled were:
Of these, only the Oxford/AstraZeneca, Pfizer/BioNTech, Moderna and Janssen vaccines are currently licensed for use in the UK. Half-doses of Pfizer/BioNtech, Novavax and Valneva were also tested.
Led by University Hospital Southampton NHS Foundation Trust (UHS), the trial recruited over 2,800 participants aged 30 or over through National Institute for Health Research (NIHR)-supported sites including one co-hosted by the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust.
Professor Saul Faust, trial lead and Director of the NIHR Clinical Research Facility at UHS, said: “Our side effect data shows all seven vaccines are safe to use as a third dose, with acceptable levels of ‘reactogenicity’ – inflammatory side effects like injection site pain, muscle soreness, fatigue. All seven boosted levels of spike protein antibodies significantly after two doses of the Oxford/AstraZeneca vaccine. However, only six also did so after two doses of Pfizer/BioNTech, (Oxford/AstraZeneca, Pfizer/BioNTech, Moderna, Novavax, Janssen and CureVac). There were also large variations in response with different boosters. It’s really encouraging that a wide range of vaccines, using different technologies, show benefits as a booster dose to either of these vaccines. That gives confidence and flexibility in developing booster programmes here and globally, with other factors like supply chain and logistics also in play.”
Dr Christopher Green, Senior Clinical Lecturer at the University of Birmingham and Consultant Physician in Infectious Diseases at University Hospitals Birmingham NHS Foundation Trust, said: “We are immensely pleased to have played our part in how vaccine research can rapidly respond to the needs of the public during this pandemic. The members of the Wes Midlands public who took part in this trial, as well as the many other vaccine trials we have conducted, deserve a special thanks for joining and supporting our team of researchers, and these trials are so important as we hope to stay one step ahead of the virus.”
The study found that there were large differences in spike protein antibody levels after 28 days across the vaccines. In people who had received two initial doses of the Oxford/AstraZeneca vaccine, these ranged from 1.8 times higher to 32.3 times higher with different booster vaccines. For those who had received the Pfizer/BioNTech vaccine initially, the range was 1.3 times higher to 11.5 times higher. Booster results were similar for those aged 30 to 69 years and those aged 70 years or older.
The study also looked at immune T-cell responses. T-cells are likely to be important in controlling disease severity, although their impact on overall protection or longevity of immunity is not yet known. COV-BOOST reported T-cell responses in several combinations of initial and booster vaccines, however these were not predictable based on spike protein antibody levels.
Reactions to all seven vaccines were similar, with fatigue, headache, and injection site pain most often reported. These were more commonly reported by those aged 30 to 69. 912 of the 2,878 participants experienced a total of 1036 adverse events, only 24 of which were severe.
Prof Faust added: “It’s important to note two things about these results. First, they only relate to these vaccines as boosters to the two primary vaccinations, not how well they work as first and second doses. Secondly, the data describe the immune response at 28 days, not vaccine effectiveness. The relationship between that response and long-term protection is still poorly understood. We will be looking at the longer-term immune responses in COV-BOOST, conducting further tests at three months and one year after receiving boosters. We are also looking at whether a longer period between second and third doses improves response to the two of the booster vaccines. Several studies have shown this effect between first and second doses. We’ve done that by giving some of our original control participants the booster at a later point, and we expect those results to be available in the New Year.”
Professor Andrew Ustianowski, National Clinical Lead for the UK NIHR COVID Vaccine Research Programme, said: “Heading into the winter, and due to the emergence of the Omicron, the results from COV-BOOST are extremely timely and of national and international importance. Since the beginning of the pandemic NIHR and the NHS have been supported by the efforts and selflessness of study participants - helping us to identify the most effective vaccines and how they can be used flexibly to protect more people. We welcome the latest results from the study, and continue to support the COV-BOOST team with the further analysis of data which will help us understand the use of these vaccines as boosters long term.”
COV-BOOST was designed so that stored samples can be used in evaluating these vaccines’ effectiveness in neutralising any new variants of concern, and COV-BOOST samples have been made available to UKHSA for testing against omicron.
Notes to Editors:
- 1The MenACWY vaccine was used because it can cause similar minor side effects to ChAd and BNT, such as a sore arm, headache, and fever. Saline – which is often used as a control – does not cause any side effects.
- For interviews with Dr Chris Green, please contact Emma McKinney (Media Relations Manager, University of Birmingham).
- Media queries regarding vaccine policies following the study results, should be directed to the Department of Health & Social Care Press Office by calling 0207 972 3272.
- Munro et al (Dec, 2021). 'Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial'. The Lancet. DOI: 10.1016/S0140-6736(21)02717-3
- This study was funded by the UK Vaccine Taskforce and National Institute for Health Research.
- The University of Birmingham is ranked amongst the world’s top 100 institutions, and its work brings people from across the world to Birmingham, including researchers and teachers and more than 6,500 international students from nearly 150 countries.
- The mission of the National Institute for Health Research (NIHR) is to improve the health and wealth of the nation through research. We do this by:
- Funding high quality, timely research that benefits the NHS, public health and social care;
- Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services;
- Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research;
- Attracting, training and supporting the best researchers to tackle complex health and social care challenges;
- Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system;
- Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries.
- NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK Aid from the UK government.
- The Vaccines Taskforce (VTF) is a joint unit in the Department for Business, Energy and Industrial Strategy (BEIS) and Department for Health and Social Care (DHSC). The VTF was set up to ensure that the UK population has access to clinically effective and safe vaccines as soon as possible, while working with partners to support international access to successful vaccines. The Vaccines Taskforce comprises a dedicated team of private sector industry professionals and officials from across government who are working at speed to build a portfolio of promising vaccine candidates that can end the global pandemic. The Vaccines Taskforce’s approach to securing access to vaccines is through:
- procuring the rights to a diverse range of promising vaccine candidates to spread risk and optimise chances for success
- providing funding for clinical studies, diagnostic monitoring and regulatory support to rapidly evaluate vaccines for safety and efficacy
- providing funding and support for manufacturing scale-up and fill and finish at risk so that the UK has vaccines produced at scale and ready for administration should any of these prove successful