28 June 2021
- Mixed schedules involving Pfizer-BioNTech and Oxford-AstraZeneca generate strong immune response against SARS-CoV2 spike IgG protein
- Doses administered four weeks apart; data for 12-week dose interval due soon.
- Immune responses differed according to order of immunisation, with Oxford-AstraZeneca followed by Pfizer-BioNTech generating the better immune response out of the two mixed schedules.
Alternating doses of the Oxford-AstraZeneca and Pfizer-BioNTech vaccines generate robust immune responses against COVID-19, according to researchers running the University of Oxford-led Com-COV study.
In a paper published on the Lancet pre-print server, they report that both ‘mixed’ schedules (Pfizer-BioNTech followed by Oxford-AstraZeneca, and Oxford-AstraZeneca followed by Pfizer-BioNTech) induced high concentrations of antibodies against the SARS-CoV2 spike IgG protein when doses were administered four weeks apart.
This means all possible vaccination schedules involving the Oxford-AstraZeneca and Pfizer-BioNTech vaccines could potentially be used against COVID-19.
Professor Matthew Snape, Associate Professor in Paediatrics and Vaccinology at the University of Oxford, and Chief Investigator on the trial, said: ‘The Com-COV study has evaluated “mix and match” combinations of the Oxford and Pfizer vaccines to see to what extent these vaccines can be used interchangeably, potentially allowing flexibility in the UK and global vaccine roll-out.
‘The results show that when given at a four-week interval both mixed schedules induce an immune response that is above the threshold set by the standard schedule of the Oxford/AstraZeneca vaccine. The investigators would like to thank the participants that made this important study possible.’
Of note is that the order of vaccines made a difference, with an Oxford-AstraZeneca/Pfizer-BioNTech schedule inducing higher antibodies and T-cell responses than Pfizer-BioNTech/Oxford-AstraZeneca, and both of these inducing higher antibodies than the licensed, and highly effective ‘standard’ two-dose Oxford-AstraZeneca schedule. The highest antibody response was seen after the two-dose Pfizer-BioNTech schedule, and the highest T cell response from Oxford-AstraZeneca followed by Pfizer-BioNTech.
Professor Matthew Snape said: ‘These results are an invaluable guide to the use of mixed dose schedules, however the interval of four weeks studied here is shorter than the eight to 12-week schedule most commonly used for the Oxford-AstraZeneca vaccine. This longer interval is known to result in a better immune response, and the results for a 12-week interval will be available shortly’.
Deputy Chief Medical Officer Professor Jonathan Van-Tam said: ‘Today’s data are a vital step forward, showing a mixed schedule gives people protective immunity against COVID-19 after four weeks.
‘Equally, they offer supportive evidence that the standard (non-mixed) JCVI recommendations for COVID-19 vaccination all produce highly satisfactory immune responses, for both main vaccines in use. Given the UK’s stable supply position there is no reason to change vaccine schedules at this moment in time.
‘The results for the 12-week interval, which are yet to come, will have an instrumental role to play in decisions on the future of the UK’s vaccination programme.
‘Our non-mixed (homologous) vaccination programme has already saved tens of thousands of lives across the UK but we now know mixing doses could provide us with even greater flexibility for a booster programme, while also supporting countries who have further to go with their vaccine rollouts and who may be experiencing supply difficulties.’
Professor Andrew Ustianowski, NIHR Clinical Lead for the COVID-19 Vaccination Programme and Joint National Infection Specialty Lead, said: ‘We know that the Oxford-AstraZeneca two-dose schedule is highly effective and has helped to save many lives. The fact we now know it works well, in terms of immune responses, when combined with the Pfizer vaccine provides researchers with the valuable knowledge that these vaccines could be used flexibly for those yet to be vaccinated in the UK and globally.
‘It would have been impossible to discover these results without the willingness and efforts of research participants across the country. Yet again they have worked alongside researchers to help find an end to the spread of COVID-19.’
In May, researchers reported preliminary Com-COV data revealing more frequent mild to moderate reactions in mixed schedules compared to standard schedules, however, these were short-lived in duration.
The University of Oxford is leading the Com-COV study, run by the National Immunisation Schedule Evaluation Consortium (NISEC) and backed by £7 million of government funding from the Vaccines Taskforce.
It aims to evaluate the feasibility of using a different vaccine for the initial ‘prime’ vaccination to the follow-up ‘booster’ vaccination, helping policymakers explore whether this could be a viable route to increase the flexibility of vaccination programmes.
The trial recruited 830 volunteers aged 50 and above from eight National Institute for Health Research (NIHR) supported sites in England to evaluate the four different combinations of prime and booster vaccination.
In April, the researchers expanded the programme to include the Moderna and Novavax vaccines in a new study, run across nine National Institute for Health Research supported sites by NISEC and backed through funding from the Vaccines Taskforce and the Coalition for Epidemic Preparedness Innovations.
The six new ‘arms’ of the trial each recruited approximately 175 candidates, adding a further 1070 recruits into this programme.
Both studies are designed as so-called ‘non-inferiority’ studies – the intent is to demonstrate that mixing is not substantially worse than not mixing – and will compare the immune system responses to the gold-standard responses reported in previous clinical trials of each vaccine.
If the studies show promising results, the Medicines and Healthcare products Regulatory Agency (MHRA) and the Joint Committee on Vaccination and Immunisation (JCVI) would formally assess the safety and efficacy of any new vaccination regimen.
Notes to Editors:
To see the paper or for an interview with the lead researchers from the University of Oxford, please contact: firstname.lastname@example.org
For interviews with the lead investigators from the nine sites below, please contact these sites directly.
About the Com-Cov trial:
The nine different sites in the trial, are as follows:
- St George's University Hospitals NHS Foundation Trust
- University Hospitals Birmingham NHS Foundation Trust
- The University of Nottingham Health Service
- Liverpool School of Tropical Medicine
- University College London Hospitals NHS Foundation Trust
- Hull University Teaching Hospitals NHS Trust
- The Newcastle Upon Tyne Hospitals NHS Foundation Trust
- Guy's and St Thomas' NHS Foundation Trust
- Sheffield Teaching Hospitals NHS Foundation Trust
The study has been classified as an Urgent Public Health study by the NIHR and is being undertaken by NISEC and the Oxford Vaccine Group, with funding of £7 million from the government through the Vaccines Taskforce.
About the Oxford Vaccine Group
The Oxford Vaccine Group (OVG) conducts studies of new and improved vaccines for children and adults and is based in the Department of Paediatrics at the University of Oxford. The multidisciplinary group includes consultants in vaccinology, a Director of Clinical Trials, a Senior Clinical Trials Manager, adult and paediatric clinical research fellows, adult and paediatric research nurses, project managers, statisticians, QA manager, Clinical Trials IT and Development Lead, and an administration team. The team also includes post-doctoral scientists, research assistants and DPhil students and we work together with professionals from a range of specialities such as immunologists, microbiologists, epidemiologists, health communicators, and a sociologist, a community paediatrician, the local Health Protection team and a bioethicist.
OVG is a UKCRC registered clinical trials unit working in collaboration with the Primary Care Trials Unit at the University (registration number: 52).
About the National Institute for Health Research
The National Institute for Health Research (NIHR) is the nation's largest funder of health and care research. The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR commissions applied health research to benefit the poorest people in low- and middle-income countries, using Official Development Assistance funding.
About the Vaccines Taskforce
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 UK government has secured early access to 397 million vaccines doses through supply agreements with six separate vaccine developers. This includes agreements with:
- Pfizer/BioNTech for 100 million doses
- University of Oxford/AstraZeneca for 100 million doses
- Moderna for 17 million doses
- Novavax for 60 million doses
- Janssen for 20 million doses
- Valneva for 100 million doses
In addition, Government has a reservation agreement with GlaxoSmithKline/Sanofi Pasteur for 60 million doses and a non-binding agreement with CureVac for 50 million doses.
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
About the University of Oxford
Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the fifth year running, and at the heart of this success is our ground-breaking research and innovation.
Oxford is world-famous for research excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research sparks imaginative and inventive insights and solutions.
Through its research commercialisation arm, Oxford University Innovation, Oxford is the highest university patent filer in the UK and is ranked first in the UK for university spinouts, having created more than 200 new companies since 1988. Over a third of these companies have been created in the past three years.