Covid-19: Oxford trial to test efficacy of mix-and-match vaccines

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  • Oxford University has announced the launch of the first trial to investigate dosing with alternating Covid-19 vaccines.
  • Currently, the Oxford-AstraZeneca and Pfizer-BioNTech vaccines will be tested in the study.
  • Known as "heterologous boosting", this approach has been known to offer benefits for other vaccines in the past.


In a new Covid-19 vaccine clinical trial by the University of Oxford and the National Immunisation Schedule Evaluation Consortium (Nisec), volunteers will receive one dose of either the Oxford-AstraZeneca vaccine or the Pfizer-BioNTech vaccine at their first appointment, the institution announced on Thursday.

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At their second appointment, they will receive a jab of the alternative vaccine, while others will receive the same vaccine.

Some individuals will receive their second dose after a four-week interval and some after 12 weeks. This is to provide further evidence on whether widening the dosage gap can provide any benefit. The study will last for 13 months, the university said.

The trial is known as the Covid-19 Heterologous Prime Boost study or "Com-Cov" study. It will recruit over 800 participants over the age of 50 from eight National Institute for Health Research-supported sites in England who have not yet had a Covid-19 vaccine dose. This will be done over the next two to three weeks.

Scientists are using this approach, known as "heterologous boosting", to test whether mixing vaccines offers the same, a reduced or even better protection, compared with administering the same vaccine for both shots.

With the demand and supply of Covid-19 vaccines a concern, the researchers believe the findings of this new study may be useful for countries worldwide.

Could offer protection against new variants

With new variants constantly emerging - and the 501Y.V1 (first identified in the UK), 501.V2 (first identified in SA) and 501Y.V3 (first discovered in Brazil) variants fuelling concerns about vaccine resistance - giving participants two different vaccines might offer stronger protection against it.

"If we do show that these vaccines can be used interchangeably in the same schedule, this will greatly increase the flexibility of vaccine delivery and could provide clues as to how to increase the breadth of protection against new virus strains," said Matthew Snape, the chief investigator of the trial.

Snape referenced evidence from mice studies that combined adenoviral vector vaccine technology (such as the one used for the Oxford jab) with a messenger RNA vaccine (used for the Pfizer/BioNTech jab), which could generate a better response.

If approved, the Novavax and Janssen (the vaccine arm of Johnson & Johnson) vaccines are likely to be added to the trial.

Second-dose delay

Participants will undergo regular blood tests so that researchers can assess their antibody and T-cell (which finds and destroys infected cells) levels after vaccination.

According to preliminary data released this week, delaying the second dose of the Oxford vaccine by at least three months could be more effective than administering the jabs after a four-week interval.

"Given the inevitable challenges of immunising large numbers of the population against Covid-19 and potential global supply constraints, there are definite advantages to having data that could support a more flexible immunisation programme, if needed and if approved by the medicines regulator," said Professor Jonathan Van-Tam, deputy chief medical officer for England and the senior responsible officer for the study.

"It is also even possible that by combining vaccines the immune response could be enhanced, giving even higher antibody levels that last longer. Unless this is evaluated in a clinical trial, we just won't know. This study will give us greater insight into how we can use vaccines to stay on top of this nasty disease," Van-Tam added.

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