In-Depth: Why COVID vaccine mix-ups might actually be a good thing

A California woman accidentally got a dose of the Moderna COVID-19 vaccine after previously receiving Pfizer.
Posted at 4:17 PM, May 07, 2021
and last updated 2021-05-07 21:22:39-04

SAN DIEGO (KGTV) -- The instructions from the Centers for Disease Control and Prevention are clear: avoid mixing COVID vaccines.

But over the past few weeks, there have been several instances where people showed up for Pfizer and accidentally got Moderna, or the other way around.

Although the science is still early, doctors say this kind of vaccine mix-up almost certainly isn’t harmful. In fact, mixing and matching shots may have benefits.

Using a one-two punch containing different vaccine recipes isn’t a new idea: doctors call it a heterologous prime-boost. The technique is already used in a vaccine against ebola and Russia’s Sputnik V COVID vaccine.

The idea is that different vaccines train the immune system differently. And by mixing up the vaccine technology, it keeps the body on its toes.

“Whether you're on a sports team or whether you're in the military, you drill to make the scenario as real as it can be,” said Dr. Christian Ramers of Family Health Centers of San Diego. “This is kind of just mixing up the drills and maybe making your army or your sports team a little bit better prepared.”

Researchers in the United Kingdom are testing all kinds of mix-and-match combinations in the Com-Cov trial, which stands for Comparing COVID-19 Vaccine Schedule Combinations.

The first round of testing is studying a series of AstraZeneca and Pfizer vaccines, with initial results expected as early as this month. The second round involves various combinations of AstraZeneca, Pfizer, Moderna and Novavax.

Scientists theorize the best results may come from mixing different vaccine technologies, because some platforms are better at waking up one part of the immune system or another.

“For example, you may have better antibody responses when you do a certain approach. Or you may have better T cell responses when you do a certain approach. All that science has to be worked out,” said Dr. Ramers.

Pfizer and Moderna are both mRNA vaccines. This platform uses messenger RNA code wrapped in tiny fat bubbles to train the immune system. AstraZeneca and Johnson and Johnson are viral vector vaccines, which use harmless adenoviruses to transport genetic instructions. Novavax is a protein subunit vaccine, which means it introduces prebuilt fragments that look like the virus’ spike protein, not simply the instructions.

Early studies on mice suggest mixing COVID-19 platforms produces a more robust immune response.

On its website, the CDC says "every effort should be made" to avoid mixing vaccines because "the safety and efficacy of a mixed-product series have not been evaluated." Individuals who accidentally receive a dose of a different product, however, should be considered fully vaccinated and do not need further shots.

In the coming months, the question of mixing and matching will be important if we need booster shots. The National Institutes of Health plans to launch a study on the safety and efficacy of mixing brands.

Dr. Ramers said the theoretical risk of harm of such mixing is low.

“There's a certain proportion of the population that won't respond to a hepatitis B vaccine. And if we just switch to a different brand sometimes people do,” he said. “So we may eventually mix and match.”