Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, says Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minnesota.
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 US 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," says Poland, who reports that he 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.
Poland tells Medscape Medical News 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 Monday, 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, Poland points 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 (CDC) 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, Poland says, although human trials have not proven that, he acknowledges.
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 EUA?
Although hesitant to make recommendations to his patients, Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado in Aurora, says matching vaccine platforms might not be the preferred vaccination strategy.
He disagrees that there's a lack of science surrounding the issue, and says all signs point to mixing as not only a good option, but probably a better one.
Researcher Says Science Backs Mixing
A mix of two different vaccine platforms likely enhances immunity, Kedl says. The heterologous prime-boost strategy has been used in animal studies for decades, "and it is well known that this promotes a much better immune response than when immunizing with the same vaccine twice," Kedl explains.
"If you think about it in a Venn diagram sort of way, it makes sense," he tells Medscape Medical News. "Each vaccine has a number of components in it that influence immunity in various ways, but between the two of them, they only have one component that is similar. In the case of the coronavirus vaccines, the one thing both have in common is the spike protein from SARS-CoV-2. In essence, this gives you two shots at generating immunity against the one thing in each vaccine you care most about, but only one shot for the other vaccine components in each platform, resulting in an amplified response against the common target."
In fact, the heterologous prime-boost vaccination strategy has proven to be effective in humans in early studies.
For example, an Ebola regimen that consisted of an adenovirus vector, similar to the AstraZeneca COVID vaccine, and a modified vaccinia virus vector showed promise in a phase 1 study. And an HIV regimen that consisted of the combination of a DNA vaccine, similar to the Pfizer and Moderna mRNA vaccines, and another viral vector showed encouraging results in a proof-of-concept study.
In both these cases, the heterologous prime-boost strategy was far better than single-vaccine prime-boost regimens, Kedl points out. And neither study reported any safety issues with the combinations.
For now, it's best to stick with the same manufacturer for both shots, as the CDC guidance suggests, he says, agreeing with Poland.
But "I would be very surprised if we didn't move to a mixing of vaccine platforms for the population," Kedl says.
Marcia Frellick is a freelance journalist based in Chicago . She has previously written for the Chicago Tribune, Science News and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud ( Minnesota ) Times. Follow her on Twitter at @mfrellick.