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While the data remain preliminary, some countries are moving ahead with mixing and matching mRNA and adenoviral vector COVID-19 vaccines, often driven by supply challenges.

Germany has recently made an to mix-and-match, encouraging citizens to follow their AstraZeneca shots with a dose of an mRNA vaccine. Chancellor Angela Merkel led the way by following her initial AstraZeneca dose with .

Other countries like and have started administering vaccines on a heterologous schedule.

The European Medicines Agency (EMA) and the European Centre for Disease Prevention and Control (ECDC), while not issuing any specific recommendations, promoted the mix-and-match approach in a recent .

"There are good scientific grounds to expect this strategy to be safe and effective when applied to vaccination against COVID-19," the press release stated. "Preliminary results from studies in Spain, Germany, and the U.K. suggest a satisfactory immune response and no safety concerns. More data are awaited shortly, and EMA will continue to review these as they become available."

The EMA and ECDC noted in the release that the approach "may allow populations to be protected more quickly and make better use of available vaccine supplies."

Neither the World Health Organization (WHO) nor the CDC endorse the approach, however.

Currently, the CDC's states that getting an adenoviral vector vaccine after the first dose of an mRNA shot could be considered only "in limited, exceptional situations." Additionally, because the U.S. still has ample vaccine supply, the rush to start offering the mix-and-match approach isn't as much of a necessity as it is in countries that to struggle for access.

WHO's chief scientist Soumya Swaminathan, MD, said in an online briefing that the trend toward mixing and matching could lead to a "chaotic situation," reported. She later wrote in a that the future of the heterologous approach should be decided by public health agencies.

"Data from mix-and-match studies of different vaccines are awaited," she said. "Immunogenicity and safety both need to be evaluated."

The preliminary evidence cited by health agencies that have adopted the strategy includes Oxford's , which was submitted to the Lancet's preprint server. The single-blind randomized trial in 830 participants found that mixing Pfizer and AstraZeneca produced a more robust antibody response than two doses of AstraZeneca.

Similar results were seen in recent . A conducted by a team from Saarland University in Hamburg found that "in all parameters that we looked at, [the heterologous regimen] was similar or superior to the homologous mRNA regimens," co-author and immunologist Martina Sester, PhD, told 番茄社区app.

"What was strikingly different to both homologous regimens was that the T cells were significantly better [in the heterologous regimen] than both the homologous Astra and the homologous mRNA regimen," she said.

Gregory Poland, MD, of the Mayo Clinic's vaccine research group, told 番茄社区app that mixing and matching on a large scale is "pretty much inevitable."

"Many people will not know what [vaccine] they got and many locales won't necessarily have good records," Poland said. "So, by necessity and practicality, it's going to happen."

He noted that there's still much to learn about the safety to mixing and matching, however. Findings from the Com-COV study suggested the strategy may increase symptoms such as chills, fatigue, headaches, and muscle aches. It's also possible that there could be rare adverse events resulting from a mix-and-match strategy, he said, but it would take time and millions of doses to find that out.

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