Vaccine mismatch: What to do after dose 1 when plans change


Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, said Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minn.

Dr. Gregory Poland, a vaccinologist at the Mayo Clinic in Rochester, Minnesota

Dr. Gregory Poland

After all, that’s how they were tested for efficacy and safety, and it was results from those studies that led to emergency use authorization (EUA) being granted by the Food and Drug Administration.

But states and countries have struggled to keep up with the demand for vaccine, and more flexible vaccination schedules could help.

So researchers are exploring whether it is safe and effective to get the first and second doses from different manufacturers. And they are even wondering whether mixing doses from different manufacturers could increase effectiveness, particularly in light of emerging variants.

It’s called the “interchangeability issue,” said Dr. Poland, who has gotten a steady stream of questions about it.

For example, a patient recently asked about options for his father, who had gotten his first dose of the AstraZeneca vaccine in Ecuador, but had since moved to the United States, where that product has not been approved for use.

Dr. Poland said in an interview that he prefaces each answer with: “I’ve got no science for what I’m about to tell you.”

In this particular case, he recommended that the man’s father talk with his doctor about his level of COVID-19 risk and consider whether he should gamble on the AstraZeneca vaccine getting approved in the United States soon, or whether he should ask for a second dose from one of the three vaccines currently approved.

On March 22, 2021, AstraZeneca released positive results from its phase 3 trial, which will likely speed its path toward use in the United States.

Although clinical trials have started to test combinations and boosters, there’s currently no definitive evidence from human trials on mixing COVID vaccines, Dr. Poland pointed out.

But a study of a mixed-vaccine regimen is currently underway in the United Kingdom.

Participants in that 13-month trial will be given the Oxford/AstraZeneca and Pfizer/BioNTech vaccines in different combinations and at different intervals. The first results from that trial are expected this summer.

And interim results from a trial combining Russia’s Sputnik V and the AstraZeneca vaccines are expected in 2 months, according to a Reuters report.

Mix only in ‘exceptional situations’

The Centers for Disease Control and Prevention has been hesitant to open the door to mixing Pfizer and Moderna vaccinations, noting that the two “are not interchangeable.” But CDC guidance has changed slightly. Now, instead of saying the two vaccines should not be mixed, CDC guidance says they can be mixed in “exceptional situations,” and that the second dose can be administered up to 6 weeks after the first dose.

It is reasonable to assume that mixing COVID-19 vaccines that use the same platform – such as the mRNA platform used by both the Pfizer and Moderna vaccines – will be acceptable, Dr. Poland said, although human trials have not proven that.

However, it is unclear whether vaccines that use different platforms can be mixed. Can the first dose of an mRNA vaccine be followed by an adenovirus-based vaccine, like the Johnson & Johnson product or Novavax, if that vaccine is granted an EUA?

Dr. Ross Kedl, a vaccine researcher and professor of immunology at the University of Colorado in Aurora

Dr. Ross Kedl

Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado at Denver, Aurora, said matching vaccine platforms might not be the preferred vaccination strategy.

He disagreed that there’s a lack of science surrounding the issue, and said all signs point to mixing as not only a good option, but probably a better one.


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