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Potential Benefits of Mixing and Matching Coronavirus Vaccines

coronavirus vaccines
Some people opt in to receive different COVId-19 vaccines. Credit: Retha Ferguson / (CC BY 2.0)

As Europe and the rest of the world continue on a rapid vaccine rollout, a new tactic has emerged– giving two different coronavirus vaccines to people in an effort to achieve even greater immunity against the virus.

Some countries are beginning to encourage the practice — including Germany, where Chancellor Angela Merkel is among those who received a first injection of the Pfizer vaccine and the second with the Moderna product.

The majority of coronavirus vaccines are given in a two-dose series; one of the most notable exception to this rule is the Johnson & Johnson product, which is in the form of only one shot.

Until recently, it was protocol to administer the same product for each dose.

But now, a mix and match approach is being encouraged. On Tuesday, German Chancellor Angela Merkel received her second vaccine, which was of a different kind than her first inoculation.

The news that the veteran German politician was taking the decision to use a different vaccine product has piqued interest around the globe.

Merkel’s spokesman, Steffen Seibert, suggested to the press that the Chancellor’s choice was in part meant to set an example.

Most European countries, including Germany, resumed the use of the AstraZeneca product a few weeks after it was paused this Spring after thrombosis developed in recipients.

When Merkel received the AstraZeneca shot in April, many still remained deeply skeptical of it, creating a problem during the rollout of the vaccination campaign.

Seibert told reporters on Wednesday “With her first vaccination with AstraZeneca, the chancellor was possibly able to encourage many people to get vaccinated with AstraZeneca.”

Germany’s vaccine authorities had recommended back in April that all those under 60 who had received the AstraZeneca product first should follow it up with either a Pfizer or Moderna shot.

The regulators backed off on that advice this month, but the German chancellor, who is 66, received the Moderna vaccine on Tuesday; as Seibert noted  “Perhaps she can also relieve people of their worries about a so-called ‘cross-vaccination’ by getting one herself.”

However, it remains unclear why Merkel would have received the Moderna product since the Pfizer/BioNTech product is partially a German vaccine, with the small German BioNTech firm creating the formulation for it.

Just what are the advantages of mixing and matching coronavirus vaccines?

As a result of vaccine shortages, some nations have been forced to use different brand of vaccine, but thus far, American regulators have been wary of encouraging the practice as a rule.

But now, scientists and health officials are looking into the possible advantages of giving different inoculations to the public, including stronger immunity.

The mixing of vaccines, called “heterologous prime-boost,” is not a new concept, with researchers experimenting with it in their fight against the Ebola virus.

The thought behind the concept is that the slight differences between the vaccines could generate a stronger immune response.

This may be because they stimulate slightly different parts of the immune system; additionally it could be because the vaccines are designed to teach the body to recognize different parts of a virus that is introduced to the body.

John Moore, a virologist at Weill Cornell Medicine, explains to the New York Times “The argument is that one and one makes three. How well that argument holds up in practice in the Covid area is going to need to be judged by the actual data.”

Zhou Xing, an immunologist at McMaster University in Ontario, Canada, is onboard with the concept, saying that on top of the immunity benefits, mixing and matching vaccines  “offers much-needed flexibility when vaccine supplies are uneven or limited” in certain areas.

A number of clinical trials are now ongoing as researchers around the world try to determine the efficacy of the practice.

Teams at the University of Oxford are now trialing different combinations of vaccines, including the AstraZeneca-Oxford, Pfizer-BioNTech, Moderna and Novavax inoculations, in a test called the Com-Cov trial.

The U.S. National Institutes of Health recently started a trial of mixed doses as a form of booster shots.

Even Russia, which came out with its own coronavirus vaccine, called Sputnik V, are now testing a combination of that and the AstraZeneca inoculation, which is one of the more commonly given shots in Europe although it has not received the go-ahead by the US’ Food and Drug Administration.

The concept is certainly not foreign to the Russian scientists, since the Sputnik V shot itself has a slightly different formulation between the first and second doses.

Already the tests are showing that there may be distinct advantages in the mixing and matching of vaccines.

Most studies are still in the preliminary weeks and months of trials, but some researchers have already released promising results from them.

In May, Spanish researchers announced their findings that those who had received a dose of the AstraZeneca product, followed by a dose of the Pfizer vaccine, demonstrated a strong immune response.

Importantly, this mixing and matching appeared to create a stronger immune response than two identical doses of the AstraZeneca vaccine, according to Xing. However, it is unknown if this protocol produces a more advantageous result than two doses of the Pfizer vaccine.

Preliminary results from the ongoing Com-Cov study at Oxford University appear to show that combining vaccines may actually increase the chances of subjects experiencing mild and even moderate side effects, including fever, fatigue and headache, according to the Times report.

The information gleaned so far indicates that a mix and match dosing program “might have some short-term disadvantages,” the researchers state, although it is also possible that these very same side effects could simply indicate a strong, and desirable, immune response.

Importantly, the researchers found that the majority of the reported side effects dissipated within 48 hours after inoculation.

Researchers around the world are indicating that they expect the data that emerges from the studies to demonstrate that the mix and match approach is safe for the public.

“As we’ve learned in 18 months of Covid-19 shocks, never say never, but its really hard to rationalize any new risk associated with what is really a basic, tried and tested immunological approach,” stated Daniel Altmann, an immunologist at Imperial College London.

The UK, which was the hardest hit amongst all developed nations in the pandemic, suffering 128,000 deaths out of a population of 66.65 million people, began allowing this mix and match vaccine approach early on in its inoculation campaigns as it ramped them up quickly after the AstraZeneca product hit the market.

Health officials in Germany, Canada, Sweden, France, Spain and Italy, have all ruled that those who received one dose of the AstraZeneca vaccine, which has been repeatedly linked to thrombosis, can get a different vaccine for their second inoculation.

The nation of South Korea, experiencing delays in AstraZeneca vaccine deliveries, ruled last week that health care professionals who had received a first AstraZeneca shot could receive the Pfizer inoculation to complete their vaccination series.

The vaccine advisory panel for the nation of Canada has also now ruled that heathcare professionals can now use the Pfizer and Moderna inoculations interchangeably.

However, US officials are more wary of mixing and matching, as shown in its recent statement saying that this who received one dose of either the Pfizer or Moderna vaccine may receive a second dose of the other in what they termed “exceptional situations,” including when the original vaccine is unavailable.

Dr. Moore, of Weill Cornell, states that “I cannot imagine that the FDA will allow this kind of mix-and-match strategy without properly evaluating clinical trial data.”

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