Emily Anthes

Several countries are allowing people to receive different doses of vaccines, a technique that scientists hope will have benefits. German Chancellor Angela Merkel is one of the people who underwent this combination of drugs.

The most widely used vaccines against coronavirus are designed to be administered as two-dose inoculations, and almost all vaccinated people have received injections of the same vaccine.

But that is changing because more countries are allowing and, in some cases, encouraging, combined inoculation, with people receiving the first dose of one vaccine and then a second injection of a different one. On Tuesday, the German government revealed that Chancellor Angela Merkel had received doses of two different vaccines, adding to the growing interest in the practice.

Some nations have tried to take that approach out of necessity, when supplies of a particular vaccine were in short supply; or as a precaution, when questions were raised about the safety of a vaccine after a group of people had already received their first doses. So far, US regulators have been reluctant to encourage such a practice.

But scientists and health policy makers are interested in the possibility that giving different injections to the same person could have significant benefits. Here are some frequently asked questions about combination vaccination.

What are the potential benefits?

Mixing vaccines (scientists define it as “heterologous primary booster”) is not a new idea, and researchers have already experimented with this technique to combat other diseases such as Ebola.

Scientists have theorized that giving two slightly different vaccines could elicit a stronger immune response, perhaps because the vaccines stimulate only slightly different parts of the immune system or teach you to recognize different parts of an invading pathogen.

“The argument is that one and one equals three,” said John Moore, a virologist at Weill Cornell Medicine. “Knowing if that argument holds up when we refer to COVID-19 is something that will have to be judged by the real data.”

In addition to potential immune benefits, combining and pairing also “offers much-needed flexibility when vaccine supplies are uneven or limited,” said Zhou Xing, an immunologist at McMaster University in Canada.

What does the data say?

Multiple clinical trials are currently underway to determine whether there are benefits or drawbacks. Researchers at the University of Oxford are testing different vaccine combinations – including AstraZeneca-Oxford, Pfizer-BioNTech, Moderna and Novavax injections – in the Com-Cov trial, and the US National Institutes of Health also started a trial with doses mixed reinforcement.

Russian researchers are testing a combination of their Sputnik V vaccine and the AstraZeneca injection. Sputnik itself is based on a mix-and-match approach because the first and second doses have different formulas.

Most of the studies are still in the early stages, but some have published promising preliminary results. Last month, for example, a team of Spanish researchers announced that people who received a dose of the AstraZeneca vaccine, followed by a dose of Pfizer, showed a strong immune response.

It appears that that combination elicited a stronger immune response than two doses of AstraZeneca’s vaccine, Xing said. It is not yet clear whether it is better than two doses of Pfizer’s vaccine.

Is it safe to combine the doses?

Preliminary data from the Com-Cov study suggests that mixing and matching vaccines can increase the chances of mild and moderate side effects such as fever, fatigue, and headache.

The data suggests that “could have some short-term downsides,” the researchers wrote, although it’s also possible that the side effects are a sign of a strong immune response. Most of the side effects disappeared within 48 hours.

Overall, scientists believe the data could confirm that the technique is safe. “As we have learned in these 18 months of battles against COVID-19, never say never, but it is difficult to rationalize any new risks that are associated with what is a basic, tried and tested immune approach,” said Daniel Altmann, immunologist at the Imperial College London, in an email.

Where is this technique being implemented?

Health authorities in several countries are allowing a certain degree of mixing and matching. The UK started allowing vaccine mixing from the first days of the vaccination campaign.

Officials in several countries – including Germany, Canada, Sweden, France, Spain and Italy – have said that people who received a dose of the AstraZeneca vaccine, which has been linked to a rare blood clotting disorder, may receive a different vaccine for your second dose. Due to the delay in AstraZeneca deliveries, South Korea announced last week that healthcare workers who had received a first dose of that vaccine could receive the injection from Pfizer as a second dose.

Canada’s vaccine advisory panel has also said that the Pfizer and Moderna vaccines can be used interchangeably.

The US Food and Drug Administration (FDA) has been more conservative. That agency says that people who received one dose of the Pfizer or Moderna vaccines can receive a second dose of the others in “rare situations,” such as when the original vaccine is not available.

“I don’t think the FDA will allow this combination strategy without evaluating the clinical trial data,” Moore said.

Why did Angela Merkel receive two different vaccines?

Germany protects medical privacy fiercely, but Merkel’s spokesperson Steffen Seibert suggested that, in part, combining her vaccines was made to set an example.

Isolated reports of abnormal clotting and bleeding prompted many European countries to discontinue use of the AstraZeneca vaccine in March. Most of them, including Germany, resumed use a few weeks later, after a review by the European Union’s drug regulator.

But when Merkel received the AstraZeneca injection in April, many people were deeply skeptical about it, slowing down the vaccination campaign.

“It is possible that with her first dose of AstraZeneca, the chancellor encouraged many people to inject themselves with that vaccine,” Seibert told reporters on Wednesday.

In April, Germany’s vaccine commission recommended that anyone under the age of 60 who had received the first dose of AstraZeneca should continue their process with Pfizer or Moderna. Regulators relaxed that advice this month but Merkel, 66, received the Moderna vaccine a few days ago.

“Perhaps it can also alleviate many people’s concerns about so-called ‘cross-vaccination’ because she underwent it herself,” Seibert said.

It is not yet known why he received Moderna despite the fact that in Germany great national pride has been generated by the work of BioNtech, a German company.

Moore, the Weill Cornell researcher, said he saw no problem mixing vaccines, but was curious to know what the experts advised Merkel. He also said he doubted the possibility that a US president would have done the same at this stage of the pandemic because the extremely cautious country’s regulators have not yet approved such a technique. c. 2021 The New York Times Company

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