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Study supports flexible second dose options following Pfizer or Oxford-AstraZeneca jabs

Following up first doses of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines with second doses of the Moderna and Novovax jabs will generate robust immune responses against COVID-19, according to the Com-COV 2 study led by researchers at the University of Oxford.

In a paper published in the Lancet, they report that participants receiving a first dose of Oxford-AstraZeneca or Pfizer-BioNTech generated a strong immune response when immunised nine weeks later with a second dose of COVID-19 vaccines manufactured by Novavax or Moderna. 

1,070 participants were involved in the national study, conducted across nine National Institute for Health Research-supported sites. There were no safety concerns raised.

Combination aids quicker supply 

The study supports flexible use of these vaccines in primary immunisation schedules, which is crucial to help rapid deployment, especially in low- and middle-income countries where vaccine supply may be inconsistent.

The study was designed as a non-inferiority study – the intent is to demonstrate that mixing is not substantially worse than the standard schedules – and compares the immune system responses with the gold-standard responses reported in previous clinical trials of each vaccine.

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 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.”

First jab affects immune response 

The primary vaccine had an impact on the immunogenicity of the various combinations:

  • 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 lower antibody and T-cell responses than two-dose Pfizer-BioNTech schedule, although this combination still induced higher antibodies than the two-dose Oxford-AstraZeneca 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 with those who received two doses of either Oxford-AstraZeneca or Pfizer-BioNTech.

Informing the future of immunisation

Professor 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.”

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 these 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 more populations to be better protected from COVID-19.”