Mix and match coronavirus vaccines produce robust immune response, study suggests

Doctor drawing up Covid-19 vaccine from glass phial bottle and filling syringe injection for vaccination. Close up of hand wearing protective disposable gloves in lab and holding a bottle of vaccination drugs. Hand with blue surgical gloves taking sars-coV-2 vaccine dose from vial with syringe: prevention and immunization concept.
Mixing and matching vaccines against COVID-19, the disease caused by the coronavirus, may give more 'flexibility' in the case of jab shortages. (Stock, Getty Images)

Mixing and matching different coronavirus vaccines may bring about a more robust immune response than the standard same dose regimen, research suggests.

Scientists from the UK's National Immunisation Schedule Evaluation Consortium (NISEC) are investigating the effects of administering the Pfizer-BioNTech vaccine as a first dose, followed by a University of Oxford-AstraZeneca second jab, and vice versa.

While these are not the regimens on which the vaccines were approved, many are optimistic alternating doses may lead to a more potent immune response. The NISEC team has previously reported, however, a mix and match approach may cause more side effects.

Preliminary data now reveal administering the Oxford-AstraZeneca vaccine followed by the Pfizer-BioNTech jab four weeks later led to antibody levels that were around nine times higher than after two Oxford-AstraZeneca jabs.

Antibodies were lower when the Pfizer-BioNTech vaccine was given four weeks before the Oxford-AstraZeneca jab, compared to two Pfizer-BioNTech doses, however.

Nevertheless, giving the Pfizer-BioNTech jab followed by a Oxford-AstraZeneca vaccine still led to antibody levels that were around five times higher than after two Oxford-AstraZeneca doses – with the latter being up to 90% effective at warding off severe disease.

Read more: 45-week gap between Oxford coronavirus jabs triggers 'enhanced immune response'

While there is no "magic antibody level" that protects against coronavirus complications, the more infection-fighting immune cells a person has in their blood, the less vulnerable they are expected to be.

Lead investigator Professor Matthew Snape has stressed the results – which have not yet been published in a peer-reviewed journal – support "flexibility" in the vaccines' administration. Nevertheless, the "default would be to stick" to the regimens the jabs were approved upon, he added.

Antibodies attacking SARS-CoV-2 virus, the conceptual 3D illustration for COVID-19 treatment, diagnosis and prevention
Mixing and matching vaccines may lead to more antibodies, infection-fighting proteins. The research is somewhat muddled, however. (Stock, Getty Images)

Speaking of the research, Professor Snape said: "It gives flexibility and resilience."

In the UK, blood clot concerns mean the Oxford-AstraZeneca vaccine is not routinely given to people under 40. The same issue has prompted Germany, France and Sweden – among others – to "advocate" for a mix and match approach in younger people.

People may also be offered an alternate second dose if the first vaccine triggered an allergic reaction.

A mix and match regimen could also be beneficial in less developed countries where vaccine supply chains may be disrupted.

"The default would be to stick to the schedules we know work," said Professor Snape.

Nevertheless, he added: "If the alternative is getting nothing, [for example] if supply is disrupted, I would certainly accept a mixed one [schedule]."

Read more: Thousands report period problems after coronavirus jab

Professor Jonathan Van-Tam – the UK's deputy chief medical officer – agreed, adding: "Today's data are a vital step forward, showing a mixed schedule gives people protective immunity against COVID-19 [the disease caused by the coronavirus] after four weeks.

"Given the UK's stable supply position, there is no reason to change vaccine schedules at this moment in time.

"Our non-mixed 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".

In the ongoing 13-month study – initiated in February 2021 – 830 adults aged over 50 were randomised to receive different coronavirus vaccine schedules, either four or 12 weeks apart.

The Oxford-AstraZeneca and Pfizer-BioNTech vaccines were approved based on a three week interval between their two doses. In the UK, the interval was extended to up to 12 weeks to maximise the number of people having their first jab.

The NISEC results show receiving the Oxford-AstraZeneca vaccine followed by the Pfizer-BioNTech vaccine four weeks later was "non-inferior" to having two Oxford-AstraZeneca doses.

The same was not true for Pfizer-BioNTech followed by Oxford-AstraZeneca, compared to a double Pfizer-BioNtech dose. Nevertheless, this mix and match approach led to more antibodies than administering two Oxford-AstraZeneca jabs.

Read more: Vaccines 'still offer substantial protection' against Delta variant

"It didn't pass the statistical test but clinically it did," said Professor Snape.

Both of the mix and match approaches also led to higher levels of T cells, another aspect of the immune response. This was most pronounced when an Oxford-AstraZeneca jab was followed by a Pfizer-BioNTech vaccine.

"Despite the [Pfizer-BioNTech then Oxford-AstraZeneca] regimen not meeting non-inferiority criteria" it led to antibody levels "higher than that of a licensed vaccine schedule [two Oxford-AstraZeneca doses] with proven efficacy against disease and hospitalisation", wrote the scientists.

"These data support flexibility in the use of heterologous prime-boost vaccination", they added.

The effects of a mix and match approach with a 12-week interval are pending.

"This longer interval is known to result in a better immune response and the results for a 12-week interval will be available shortly," said Professor Snape.

The scientists measured antibodies against the coronavirus' spike protein, which it uses to infect cells. Antibody levels were only recorded against the coronavirus variant that emerged in Wuhan, China, at the end of 2019 – not any of the later variants of concern.

Variants of concern will be tested against the mix and match approach at a 12-week interval, the scientists have said.

The team will also investigate the effects of administering an Oxford-AstraZeneca or Pfizer-BioNTech vaccine followed by a Moderna jab – which was only recently rolled out – or a Novavax dose, which is not yet approved in the UK.

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