7 December 2021
First dose of Oxford-AstraZeneca or Pfizer-BioNTech followed nine weeks later by second dose of Novavax or Moderna COVID-19 vaccines generated a robust immune response.
- Oxford-AstraZeneca followed by Moderna/Novavax schedules induced higher antibodies and T-cell responses than two-dose Oxford-AstraZeneca schedule.
- Pfizer-BioNTech/Moderna induced higher antibody and T-cell responses than two-dose Pfizer-BioNTech schedule
- Pfizer-BioNTech/Novavax induced higher antibodies than two-dose Oxford-AstraZeneca schedule; this schedule induced lower antibody and T-cell responses than two-dose Pfizer-BioNTech schedule.
Following up first doses of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines with second doses of the Moderna or Novavax jabs will generate robust immune responses against COVID-19, according to researchers running the University of Oxford-led Com-COV study.
In a paper published in the Lancet, they report that participants receiving a first dose of Oxford-AstraZeneca or Pfizer-BioNTech generated a robust immune response when immunised nine weeks later with a second dose of COVID-19 vaccines manufactured by Novavax or Moderna. No safety concerns were raised in this study of 1,070 participants, who took part in the study across nine National Institute for Health Research-supported sites.
This study therefore supports flexible use of these vaccines in primary immunisation schedules, which is crucial to help rapid deployment of these vaccines, especially in low- and middle-income countries where vaccine supply may be inconsistent.
Professor Matthew Snape, Associate Professor in Paediatrics and Vaccinology at the University of Oxford, and Chief Investigator on the trial, said: ‘Thanks to studies such as these, we are now getting a more complete picture of how different COVID-19 vaccines can be used together in the same vaccine schedule.
‘Encouragingly, all these schedules generated antibody concentrations above that of the licensed and effective two dose Oxford-AstraZeneca schedule. When it comes to cellular immunity, having a first dose of the Oxford-AstraZeneca vaccine followed by any of the other study vaccines generates a particularly robust response.
‘It’s only through the inspiring efforts of the Com-COV2 participants and study teams that we can generate these data; this will help get the world immunised against COVID-19 as quickly as possible.’
Of note is that the primary vaccine made a difference to the immunogenicity of the various schedules:
- Oxford-AstraZeneca followed by Moderna/Novavax schedules both induced higher antibodies and T-cell responses than the licensed and highly effective ‘standard’ two-dose Oxford-AstraZeneca schedule.
- Pfizer-BioNTech/Moderna induced higher antibody and T-cell responses than the standard two-dose Pfizer-BioNTech schedule
- Pfizer-BioNTech/Novavax induced higher antibodies than the two-dose Oxford-AstraZeneca schedule; this schedule induced lower antibody and T-cell responses than the two-dose Pfizer-BioNTech schedule.
- Blood samples taken from participants were tested for their effectiveness against the Wild-Type, Beta and Delta variants – while it was observed that the vaccines’ efficacy against the variant strains had decreased, this was a consistent trend across the mixed schedules.
In addition, a significantly higher number of short-lived vaccine reactions were reported in volunteers who received a second dose of Moderna compared to those who received two doses of either Oxford-AstraZeneca or Pfizer-BioNTech.
Professor Matthew Snape said: ‘Using different types of vaccines within the same schedule as we have done here (for example mRNA vaccines, viral-vector vaccines or protein-based vaccines) is a relatively novel approach to immunisation.
‘As well as providing evidence for flexibility in deployment, these results suggest this approach can also help generate better immune responses. This has implications beyond COVID-19 and will inform new approaches to immunisation against other diseases that are, as yet, not vaccine preventable.’
The study was designed as a so-called ‘non-inferiority’ study – the intent is to demonstrate that mixing is not substantially worse than the standard schedules – and compares the immune system responses to the gold-standard responses reported in previous clinical trials of each vaccine.
Professor Andrew Ustianowski, National Clinical Lead for the UK NIHR COVID Vaccine Research Programme, said: ‘We really cannot thank the volunteers and staff involved in studies such as Com-COV2 enough. The continued effort from everyone within the study helps to gather more important information on the immune response of vaccine dose combinations.
‘This is another set of positive findings discovered by the UK research community, supported by the NIHR, which could be applied globally. Results such as these will help to shape guidance nationally and internationally, allowing populations to be better protected from COVID-19.’
A brief Com-COV timeline
The University of Oxford is leading the Com-COV1 and Com-COV2 studies, run by the National Immunisation Schedule Evaluation Consortium (NISEC) and backed by £9.2 million of government funding from the Vaccines Taskforce. The Coalition for Epidemic Preparedness Innovations (CEPI) is providing an additional £5 million in funding for Com-COV2.
Data from the original COMCOV study in adults has shown that mixed schedules involving Pfizer-BioNTech and Oxford-AstraZeneca induced high concentrations of antibodies against the SARS-CoV2 spike IgG protein when doses were administered four weeks apart. This study has informed immunisation practices globally and already resulted in two publications in the Lancet.
In September, the programme was further expanded to test multiple options for second dose COVID-19 vaccines in young people aged 12 to 16 years.
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 or call 01865 280528.
For interviews with the lead investigators from the nine sites below, please contact these sites directly.
About the Com-Cov programme:
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 £9.2 million from the government through the Vaccine Taskforce for Com-COV1 and Com-COV2.
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 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.
About the Vaccine Taskforce
The Vaccine 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 Vaccine Taskforce is working to:
- Secure access to promising COVID-19 vaccines for the UK population as quickly as possible.
- Make provision for international distribution of vaccines.
- Strengthen the UK’s onshoring capacity and capability in vaccine development, manufacturing and supply chain to provide resilience for future pandemics.
About the University of Oxford
Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the sixth 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.