What Mixing Covid Vaccines Could Mean for the Pandemic

Most of the Covid-19 shots that have proved effective have been two-dose vaccines: People get two portions of the same formulation injected into their arm, weeks or months apart. Months into the rollout of the vaccines, a number of countries wound up administering a different second shot in some cases. Soon, some people were actively seeking out this method, citing research that says mixing vaccine types can provide an advantage. With vaccine shortages holding up a return to normalcy for much of the Covid-plagued world, mixing shots could become a strategy to help end the pandemic.

1. Why are vaccines being mixed?

It mostly happened unintentionally. In March, concerns about rare blood clots associated with AstraZeneca Plc’s vaccine triggered several nations, mainly in Europe, to pause use of the shot. Some European countries soon said health-care professionals could administer a different second dose to those in certain age groups who’d had a first AstraZeneca shot, even though this combination hadn’t been tested in clinical trials. German Chancellor Angela Merkel was among those affected by this policy, receiving a Moderna Inc. vaccine after an Astra shot. Other countries, such as Canada, have cited restricted supplies of the Astra vaccine as a reason for mixing shots. This could become more common in poorer countries struggling to secure a steady pipeline of doses. Finally, some people -- including pharmaceutical executives -- have purposefully switched up their own shots based on evidence that mixing vaccine types can produce stronger immunity.

2. What’s the potential advantage?

Mixing two vaccines of the same type -- such as those from Moderna and Pfizer Inc.’s partnership with BioNTech SE, which use an innovative technology called mRNA -- isn’t likely to give you an advantage over a standard two-dose course of one of them. But mixing vaccines that use different designs -- known as heterologous prime-boosting -- could. Different vaccine platforms activate the immune system in different ways, and some scientists think that mixing them up might generate immune responses that stimulate each other at a granular level.

3. What’s the evidence so far?

Among combinations tested in the University of Oxford’s Com-Cov trial, the two-dose course of the Pfizer vaccine produced the highest level of antibodies, which fight the virus directly. However, people who’d had an Astra shot followed by a Pfizer one had the strongest level of T cells, which stimulate antibody production and help destroy virus-infected cells. Findings released in May from a small trial in Germany suggested that mixing the Astra and Pfizer shots could trigger production of neutralizing antibodies, which block infection, at levels almost four times higher than a two-dose Pfizer course. In May, a Spanish study showed that a Pfizer shot following an Astra shot made neutralizing antibodies climb sevenfold compared with two Astra doses. What trials haven’t yet determined is which combination provokes an immune response that lasts longest and gives the best protection against variants of the coronavirus that causes Covid.

4. Has vaccine mixing been done before?

Yes. Since 2019, more than 200,000 people in Rwanda have been vaccinated against Ebola using a regulator-authorized combination of two shots with different platforms from Johnson & Johnson and Bavarian Nordic A/S. Mixing has been tested previously in clinical trials of vaccines against other diseases including HIV and hepatitis.

5. What about safety and side effects?

There’s some evidence that mixing vaccine types could cause worse side effects. According to preliminary data from the Com-Cov study, 30% to 40% of those who received mixed shots reported fevers after a second dose, compared with 10% to 20% of those who had two doses of the same vaccine. However, researchers said the fevers didn’t last long and that they had no other safety concerns. The Spanish study found only mild side effects, similar to those seen in standard dosing regimens. In the U.S., the Centers for Disease Control and Prevention has warned against mixing vaccines, saying the “safety and efficacy of a mixed-product series have not been evaluated.”

6. How could mixing help end the pandemic?

In countries where vaccine supplies are scarce, knowing people can safely and effectively mix vaccines could help overcome shortages. Freeing countries from the need to match second doses to first doses would give them more flexibility to use the vaccine that is most readily available. Moreover, if researchers can pinpoint the combination of vaccine types that will boost immunity for the longest and is most potent against variants, it could help protect populations against Covid more efficiently and reliably -- assuming production of such a superior combo could be scaled up. As governments are ordering supplies for future booster shots, it’s important to know which formulations could maximize protection, especially if it depends on which vaccines a person has already been given. Trials in the U.K. and U.S. are examining this. Finally, as pharmaceutical companies work to produce new versions of vaccines that are more effective against variants, knowing that people can safely receive a third shot that’s based on a technology different from their previous ones could ease supply concerns.

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