Alternating COVID-19 Vaccine Trial Expands to Include Moderna and Novavax

Peter Russell

April 14, 2021

A trial to assess outcomes from mixing and matching COVID-19 vaccines has been extended to include the Moderna and Novavax vaccines.

Since February, the Com-COV study, run by the University of Oxford, has been investigating alternating first and second doses of the AstraZeneca/Oxford vaccine and the Pfizer/BioNTech vaccine.

Prof Mathew Snape/SMC

Mathew Snape, associate professor in paediatrics and vaccinology at the Oxford Vaccine Group, who is chief investigator for the trials, is now seeking to recruit 1050 adults aged over 50 in England, who have already received one dose of vaccine in the NHS rollout, to take part in Com-COV 2.

Volunteers, who will have received either the Oxford/AstraZeneca or Pfizer/BioNTech vaccine, will be randomly allocated to receive either the same vaccine for their second dose, or a dose of the COVID-19 vaccines produced by Moderna or Novavax.

Trials Could Give Vaccine Programme More Flexibility

"If we can show that these mixed schedules generate an immune response that is as good as the standard schedules, and without a significant increase in the vaccine reactions, this will potentially allow more people to complete their COVID-19 immunisation course more rapidly," according to Prof Snape.

He explained in a briefing hosted by the Science Media Centre: "The way the vaccines have been licensed and approved is that people who've received the first dose of one vaccine should get that vaccine for a second dose, but that does leave you hostage to fortune when it comes to things like problems with supply, or the recommendations change."

More than 800 people are currently taking part in the original trial, with initial findings expected in May.

Early results from Com-COV 2, are likely to emerge in June or July.

Measuring Immune Responses

The non-inferiority study will compare immune responses in both antibodies and T-cells in 'same' and 'alternate' second doses.

"We're very interested in the T-cells because it may well be that they provide a key to providing protection against new variants," said Prof Snape. "Because their immune response is directed against the whole spike protein, rather than just key elements of it, they may have a broader protection against new variants that come through."

Investigators will also monitor any unexpected adverse reactions from alternating the vaccines.

Prof Snape said investigators would be asking: "Are there any combinations we shouldn't be giving, because they don't generate a good immune response – and I'm hoping that won't be the case."

A mix and match approach would "give us lots of flexibility, not just in the UK, not just in Europe, when we're looking at restricting uses of some vaccines for some age groups, but across the world, where we have, perhaps, a little bit more intermittent supply of vaccines".

France and Germany have recently recommended that some people who received a first dose of the AstraZeneca/Oxford vaccine should be given a different vaccine for their second dose.

Prof Snape said until trial results became available, there was a risk that this approach could lead to sub-optimal immune responses. "We don't know, and that's why it's important to do the study," he said.

The Com-COV 2 trial will recruit from 9 different sites across England.

UK regulators have yet to decide whether to approve the Novavax vaccine for routine NHS use, but the manufacturer will supply doses for the trial.

If the study showed promising results, the Medicines and Healthcare products Regulatory Agency and the Joint Committee on Vaccinations and Immunology would formally assess the safety and efficacy of any new vaccination regimen before it was rolled out to patients.


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