With two coronavirus vaccines now available in the UK, FactCheck readers have started to ask: is it possible to get the first dose from one manufacturer and the second from another? And is it safe?

What are the rules?

Latest advice from Public Health England (PHE) says that if “the same vaccine is not available, or if the first product received is unknown, it is reasonable to offer one dose of the locally available product to complete the schedule.” This might be necessary “if the individual is likely to be at immediate high risk” from a severe Covid infection, it adds.

The guidance was the subject of some controversy over the weekend after the New York Times published an article initially headlined “Britain Opts for Mix-and-Match Vaccinations, Confounding Experts”.

The headline and article have since been updated following a request from the British Medical Journal and the piece now quotes a PHE official saying that substitutions would on occur on “a very exceptional basis, when the alternative is to leave someone with an incomplete course [of the vaccine]”.

England’s public health officials have been keen to stress that such occasions would be “extremely rare”. And the PHE guidance also makes clear that “there is no evidence on the interchangeability of the COVID-19 vaccines” and so “every effort should be made” to match the first and second doses.

Nicola Sturgeon told MSPs yesterday that in Scotland, “the policy at this stage is that people will get both doses with the same vaccine”, unless “there were exceptional circumstances in which, for example, it was not known what vaccine had been given in the first dose.”

A spokesperson for the Welsh government told FactCheck: “It is recommended those receiving a COVID-19 vaccination should be given two doses of the same vaccine.”

So while vaccine mixing is technically allowed in Britain, it’s very much not the preferred route at the moment.

How does this compare with the US?

The NY Times article says the PHE guidance “contradicts” advice from the US Center for Disease Control and Prevention (CDC) on vaccine mixing. But on closer inspection, it seems the two are in broad agreement.

Just as PHE warns that we don’t yet know if the vaccines can be mixed, the CDC notes that even if multiple jabs are approved, this “does not necessarily indicate that [any given] vaccine is interchangeable with products from other manufacturers”.

The American authority says that the expert panel advising it on vaccine rollout “prefers that doses of vaccine in a series come from the same manufacturer”, echoing PHE’s guidance that “every effort should be made” to match doses.

And like its English counterpart, the CDC allows for the possibility of vaccine mixing in extremis: “if [matching] is not possible or if the manufacturer of doses given previously is unknown, providers should administer the vaccine that they have available.”

What happens if you mix vaccines?

The possibility of mixing vaccines is not automatically a cause for alarm – in fact, it’s sometimes even beneficial. The concept of “heterologous prime-boosting”, as it is known to experts, predates the outbreak of Covid, with early studies (in animals, as part of HIV research) dating back to 1992.

And as PHE guidance alludes to, there are already studies underway looking at whether it might help the fight against coronavirus. AstraZeneca announced last month that it is trialling its vaccine alongside the Russian Sputnik V jab.

Responding to that announcement, Helen Fletcher, professor of immunology at the London School of Hygiene and Tropical Medicine said: “This is the logical next step in vaccine development for COVID-19 as priming with one type of vaccine and boosting with another is a commonly used strategy for increasing the level and duration of efficacy against infectious disease.”

Dr Stephen Griffin, associate professor in the School of Medicine at the University of Leeds explained why. Adenovirus vaccines like the Oxford-AztraZeneca jab can “become a victim of their own success” by prompting the body to attack the “vector” that carries the second dose, he says.

“This can mean that using the same vehicle again is less effective as antibodies made as part of this ‘anti-vector’ response can reduce the efficiency of the second jab – the vehicle doesn’t get to deliver its second payload.” Using a different vaccine for the second dose might offer a way round this problem.

So would this work with the Oxford and Pfizer jabs, the two currently on offer in the UK?

Dr Griffin told FactCheck: “The only way of doing this is through clinical trials, and this would require the cooperation of the companies involved as well as approval from the MHRA (if in the UK). You could envisage more rapidly progressed large scale trials as we’ve seen already, but obviously we’d need the case to be made first”.

And as both Dr Griffin and Professor Fletcher point out, given how effective the current jabs are, it’s not clear exactly how much extra benefit we’d gain from mixing.

Professor Fletcher told FactCheck: “Heterologous prime-boost would be an important strategy to explore in clinical trials if the first generation of COVID-19 vaccines had been weakly protective, as combining vaccines could boost the level and duration of efficacy”.

But for jabs with over 90 per cent efficacy there is, she says, “little advantage” to the approach, though she adds that there might still be scope to see if it increases the length of time when people are protected.

She adds: “Based on previous studies which combine different vaccine types a combination of the [Oxford-AstraZeneca] and Pfizer vaccines is likely to be safe but it’s important that this is tested in the context of a clinical vaccine trial.”

FactCheck understands that UK researchers will begin a series of trials in the coming weeks to test various combinations of vaccines.

FactCheck verdict

New guidance from Public Health England says there is no evidence yet on whether we can mix-and-match different coronavirus vaccines and so “every effort should be made” to ensure that people get two doses of the same jab.

The same document says that if “the same vaccine is not available, or if the first product received is unknown, it is reasonable” to offer whichever jab is available, especially if the person is at high risk of serious Covid infection. Officials say such occasions would be “extremely rare”.

The Welsh government says it is “recommended” that people receive two doses from the same manufacturer.

Nicola Sturgeon said yesterday that the policy in Scotland “at this stage is that people will get both doses with the same vaccine”, unless “there were exceptional circumstances in which, for example, it was not known what vaccine had been given in the first dose.”

The British approach is broadly in line with authorities in the US, which state a clear preference for matching the first and second doses, but allow the possibility of mixing in extremis.

In principle, it’s possible that vaccine mixing could actually hold some benefits – the practice has been used against other diseases – though experts stress that tests should be carried out in formal clinical trials before we adopt the approach with Covid. At least one such study is currently underway, with more in the pipeline. We’ll have to wait for the results before we know more.