The day will come when everyone who wants a COVID-19 vaccine will be able to get one. Then people might wonder about a question that once seemed far-fetched: Should I get a second just to be safe?

As the pandemic rolls on, that actually might be an option, as more vaccines make their way through the approval pipeline in the coming months. On Friday, the U.S. Food and Drug Administration authorized emergency use of a vaccine by Moderna—just a week after it granted similar authorization for one by Pfizer and BioNTech.

More than 200 COVID-19 vaccines are in development worldwide that involve eight different technology platforms, from innovative ones made of genetic material, such as DNA or messenger RNA, to classic varieties built from inactivated versions of the coronavirus. The question is whether taking more than one type will improve your immunity and offer longer-lasting protection.

So far, double-dipping with vaccines is mostly a thought experiment. The current limited supply makes accessing two different COVID-19 vaccines unlikely unless a person sneaks into multiple clinical trials or tricks the authorized providers. And it’s unknown if health insurers would pay for more than one vaccine. But some scientists are intrigued by the possibility.

“This isn’t a ridiculous question at all,” says Florian Krammer, professor of vaccinology at Icahn School of Medicine at Mount Sinai in New York City. “We do this all the time in research. We use different vaccine platforms because, sometimes, we get interesting results.”

Maximizing the immune response
In theory, here’s how dual protection from COVID-19 vaccines would work: When you receive a vaccination, you introduce pieces of the virus that can’t make you sick—but are enough to activate an immune response.

Many traditional childhood vaccines require what’s known as a booster; another shot months or years later that acts as a reinforcement to make sure the body got the first message and has clear instructions to attack a future invasion of a specific germ. It’s a way to create another blockade of protection and strengthen one’s immunological memory.

“In cases where you’d have concern that the vaccine is losing efficacy, the most straightforward measure you would take would be to have a booster,” says Alessandro Sette, a professor at the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology in California. Yet because you’ve already received the first shot, your body already has a head start. “A booster induces a recall response. You start from immune memory. That’s the beauty of it,” Sette says.

What’s unknown is whether you’d induce an even stronger response with a different form of the coronavirus vaccine. In immunology, the concept is called a “heterologous prime-boost,” and some studies suggest that it might be a more effective way to design vaccine regimens, especially for challenging diseases such as malaria, tuberculosis, and HIV.

PHOTOGRAPH BY SERGEI MALGAVKO, TASS/ GETTY IMAGES
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Should people take more than one type of COVID-19 vaccine?
All these authorizations foretell a world with vaccine choice. Here’s what research says about whether more is better for boosting your immunity.
6 MINUTE READ
BY SARAH ELIZABETH RICHARDS

PUBLISHED DECEMBER 18, 2020

The day will come when everyone who wants a COVID-19 vaccine will be able to get one. Then people might wonder about a question that once seemed far-fetched: Should I get a second just to be safe?

As the pandemic rolls on, that actually might be an option, as more vaccines make their way through the approval pipeline in the coming months. On Friday, the U.S. Food and Drug Administration authorized emergency use of a vaccine by Moderna—just a week after it granted similar authorization for one by Pfizer and BioNTech.

More than 200 COVID-19 vaccines are in development worldwide that involve eight different technology platforms, from innovative ones made of genetic material, such as DNA or messenger RNA, to classic varieties built from inactivated versions of the coronavirus. The question is whether taking more than one type will improve your immunity and offer longer-lasting protection.

So far, double-dipping with vaccines is mostly a thought experiment. The current limited supply makes accessing two different COVID-19 vaccines unlikely unless a person sneaks into multiple clinical trials or tricks the authorized providers. And it’s unknown if health insurers would pay for more than one vaccine. But some scientists are intrigued by the possibility.

“This isn’t a ridiculous question at all,” says Florian Krammer, professor of vaccinology at Icahn School of Medicine at Mount Sinai in New York City. “We do this all the time in research. We use different vaccine platforms because, sometimes, we get interesting results.”

Maximizing the immune response
In theory, here’s how dual protection from COVID-19 vaccines would work: When you receive a vaccination, you introduce pieces of the virus that can’t make you sick—but are enough to activate an immune response.

Many traditional childhood vaccines require what’s known as a booster; another shot months or years later that acts as a reinforcement to make sure the body got the first message and has clear instructions to attack a future invasion of a specific germ. It’s a way to create another blockade of protection and strengthen one’s immunological memory.

“In cases where you’d have concern that the vaccine is losing efficacy, the most straightforward measure you would take would be to have a booster,” says Alessandro Sette, a professor at the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology in California. Yet because you’ve already received the first shot, your body already has a head start. “A booster induces a recall response. You start from immune memory. That’s the beauty of it,” Sette says.

What’s unknown is whether you’d induce an even stronger response with a different form of the coronavirus vaccine. In immunology, the concept is called a “heterologous prime-boost,” and some studies suggest that it might be a more effective way to design vaccine regimens, especially for challenging diseases such as malaria, tuberculosis, and HIV.

If you had two different vaccines that used different parts of the virus, you would make two different immune responses instead of getting a boost to the first one.

The idea is that you might benefit from the best of two vaccine platforms by eliciting different subsets of T cells, immune system agents that come in “killer” and “helper” forms and play a critical role in attacking an unwanted virus. Those divergent responses would then work in harmony to deliver rock-solid immunity.

It’s not yet clear which combinations of vaccine categories are best or in what order. But this two-method punch has been increasingly explored over the past couple of decades as scientists discovered new kinds of vaccine delivery methods.

A menu of vaccines
The science of such vaccine mixing and matching is poised to get a boost itself. That’s because this year’s flood of innovation offers new opportunities to study the interplay between the different COVID-19 vaccine types.

For example, both the Pfizer-BioNTech and Moderna vaccines inject pieces of messenger RNA, a vaccine platform that had never been authorized for human use until this month. Another candidate that’s far along in trials by the University of Oxford and the pharmaceutical company AstraZeneca uses viral-vector technology. It involves transferring the genetic code for SARS-CoV-2’s spike protein—the part that allows the coronavirus to invade cells—into a weakened adenovirus. All of these regimens are given as two doses separated by several weeks.