Vaccine cocktail: what does mixing doses mean for the fight against Covid-19?

As scientists work to see if Sputnik V and Oxford-AstraZeneca are compatible, we look at whether mixing vaccines could better protect us against new strains

Research is under way around the world to see whether mixing vaccines could offer more protection against Covid-19.

On Wednesday, Kirill Dmitriev, the head of Russia's sovereign wealth fund, said he believes pairing Sputnik V with Oxford-AstraZeneca shots could be “highly effective”.

Trials of the two are under way in several countries, including Russia. One is scheduled to run in the UAE.

And other studies are testing different “mix and match” combinations, including Pfizer-BioNTech.

Most of the vaccines against Covid-19 are administered in two doses.

But why combine different types and what are the risks?

The National explains.

The AstraZeneca-Oxford Covid-19 vaccine was approved by EU regulators in January. Reuters
The AstraZeneca-Oxford Covid-19 vaccine was approved by EU regulators in January. Reuters

Why combine vaccines?

There are a few main reasons.

First, it offers governments flexibility when supplies of one type are low.

Second, vaccines have varying levels of effectiveness against the variants. Sputnik's developers said on Wednesday the vaccine works against new strains of the coronavirus.

On state television, Alexander Gorelov, deputy head of research at Rospotrebnadzor's Institute of Epidemiology, said: "Trials have already been done in Russia and we can say with confidence that the [Sputnik V and EpiVacCoriona] vaccines registered in Russia also work against new strains."

It is not known which strains he was referring to. But trials show that the AstraZeneca vaccine offers as little as 10 per cent protection against developing mild to moderate symptoms against infection with the South African variant.

Combining two may improve protection against the virus.

Third, researchers believe using a combination of vaccines could actually strengthen immune responses by getting the best features from each.

Experiments in the UK involving mice showed that using combinations of Pfizer-BioNTech and Oxford-AstraZeneca worked well.

Offering one dose of each induced a stronger immune response than two doses of either one alone, according to Dr Matthew Snape, an associate professor in paediatrics and vaccinology at the University of Oxford, who is leading a study into the combination.

The practice of mixing vaccines has successfully been used on people before.

Immunisation programmes against Ebola, hepatitis, polio and measles, mumps and rubella in the past used different vaccinations to improve protection.

A RTA taxi driver receives Covid-19 vaccine. Courtesy: RTA
A RTA taxi driver receives Covid-19 vaccine. Courtesy: RTA

Vaccine mixing trial in UAE

In Abu Dhabi, scientists will study a combination of Sputnik and Oxford-AstraZeneca shots.

Both vaccines are known as viral vectors.

This means they use a virus – in this case a harmless cold-causing adenovirus – to carry the Sars-CoV-2 coronavirus gene to cells to deliver instructions to build antibodies against the spike.

AstraZeneca ordinarily uses only one strain of a chimpanzee adenovirus, which is administered twice.

But Sputnik uses different strains – adenovirus 26 and adenovirus 5 – of a human virus for each of the two doses.

The developers of Sputnik said the different strains were purposefully chosen to ensure the immune system does not recognise and attack the vector when the second dose is given before it has a chance to work.

It could help explain why Sputnik is more effective than AstraZeneca and why the two vaccines might work well in combination.

Because the combination uses a chimpanzee virus and a human virus, there will be no immunity built between the shots to impair the response.

Tests show Sputnik V to be 91.6 per cent effective, compared with AstraZeneca’s rate of 70 per cent.

A health worker prepares a shot of COVID-19 vaccine developed by AstraZeneca. Credit EPA
A health worker prepares a shot of COVID-19 vaccine developed by AstraZeneca. Credit EPA

How many people will the study involve?

The UAE trial will involve 100 people, all of whom will receive a combination of the Sputnik and AstraZeneca vaccines.

“Fifty subjects will receive Sputnik followed by AstraZeneca and 50 subjects will receive AstraZeneca followed by Sputnik,” said Dr Ahmed Al Hammadi, a consultant in infectious diseases at Tawam Hospital in Al Ain, at a recent public health conference.

Only the adenovirus 26 strain from Sputnik will be used.

“This provides a new way to use combinations of different vaccines, as well as to use the advantages of both vaccines,” Dr Al Hammadi said.

“The [advantage of] AstraZeneca being the chimpanzee virus is less common. We expect humans to be less exposed to it. And the Sputnik, the 26 which is, again, less common, but a human virus.”

Mixing Pfizer and AstraZeneca

In the UK, scientists are carrying out another mix-and-match trial involving two vaccines; Pfizer-BioNTech and Oxford-AstraZeneca.

It involves more than 800 people aged 50 or older and is testing a variety of combinations.

They will receive the AstraZeneca shot followed by the Pfizer vaccine, or vice versa, four or 12 weeks apart.

Unlike Sputnik and AstraZeneca, which are similar in composition, Pfizer is an entirely different type of vaccine that was built using messenger RNA technology.

Multiple doses of the Pfizer-BioNTech Covid-19 vaccine. Credit: Reuters 
Multiple doses of the Pfizer-BioNTech Covid-19 vaccine. Credit: Reuters 

Is mixing vaccines safe?

The technique has been used in the past.

However, scientists said research needs to be carried out to confirm it will work and be safe using the vaccines against Covid-19.

Speaking to The National last month, experts said long-term mixing of vaccines is unlikely to be harmful, and could even provide better protection against the virus if given as a booster later.

The practice is known as heterologous prime boosting and was used in the past to good effect.

“This has been known to greatly increase both antibody and T-cell immunogenicity when performed using certain vector combinations, above repeated dosing with the same vaccine candidate,” the World Health Organisation said in a 2014 briefing document.

But experts said combining different vaccines in the short term needs to be studied.

Prof Paul Hunter, professor of medicine and infectious diseases at the University of East Anglia, said one drug could stimulate enzymes in the liver that break down another drug, making it less effective.

“Interactions are one of the things we hammer into medical students now,” he said. “They have to be careful.”

Updated: March 18, 2021 04:53 PM

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