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.
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.
Here’s a potential reason to take multiple kinds: Some researchers are concerned about viral-vector platforms due to the possibility that a body might develop immunity to the adenovirus itself. For example, the vector used by AstraZeneca and Oxford is an adenovirus that infects chimpanzees. “We don’t have immunity against those, but we might develop immunity after the first shot,” Krammer says, in which case the second dose might be less effective.
In another scenario, Russia, Johnson and Johnson, and Chinese biotech CanSino Biologics are developing vaccines using human adenoviruses, which often cause common colds. It’s possible that people who’ve suffered many head colds over their lifetimes could already have immunity before they even receive the vaccine.
In all these cases, it might be wise to follow up with a second vaccine, like the one developed by Maryland biotechnology company Novavax that delivers bioengineered spike proteins via nanoparticles, could provide a powerful boost, Krammer says.
But the safety of any combination hasn’t been determined, and the U.S. Centers for Disease Control and Prevention recently warned against mixing the Pfizer-BioNTech vaccine with “other COVID-19 vaccine products.”
Brianne Barker, an associate professor of biology who studies immunity and viruses at Drew University in Madison, New Jersey, is among the scientists who acknowledge that it may be impossible for health officials to prevent accidental mixing of vaccine brands.
“If you went to the doctor and got one dose, you might not know that you got the Pfizer vaccine,” she says. If you went to a different provider for a second dose, you might inadvertently get the Moderna one.
A mix-up wouldn’t necessarily be dangerous, given that our bodies often encounter the same virus multiple times throughout our lifetimes. However, Barker cautions that people shouldn’t miss the second shot of their original vaccine series. “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,” she says.
Barker is also curious about whether taking two different regimens would be beneficial. “It might further boost your immune response, but whether that boost matters is not clear,” she says. “More doesn’t necessarily last longer in your body. At some point, you get enough of a response, so more doesn’t add anything.”
How long any of these COVID-19 vaccines last is a critical missing piece of the vaccine puzzle. Until that data starts to roll in, no one knows whether taking a second kind of vaccine would be a waste of time and money, or whether health insurers will cover such requests. Although the government has committed to making the initial vaccine available to all U.S. residents free of charge, it’s too early to know whether that will include future rounds with additional brands, says Karyn Schwartz, a senior fellow at Kaiser Family Foundation in Washington, D.C., who studies the COVID-19 insurance landscape.
How to know if you need another one
If you get a vaccine in the meantime, it won’t be immediately evident if your immunity to COVID-19 is waning. People who are participating in vaccine clinical trials are having their antibody levels tracked over time. Otherwise, you can get a commercial antibody test to detect when such proteins are generated in response to a vaccine or infection.
The bigger challenge is that the presence of such antibodies doesn’t necessarily mean you’re protected against COVID-19, says Dan H. Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston. Other research suggests that the lingering presence of B cells, which make antibodies, and T cells also plays an essential role. The way antibodies are currently measured in standard clinical tests may not be a good indication of immunity, says Barouch, adding: “We need to know which immune responses are responsible for protection.”
Perhaps vaccine-mediated protection against COVID-19 will last a lifetime, as it does against measles. Or, taking a second version of a vaccine may serve as a booster shot a decade down the line—similar to how the polio vaccine is sometimes given today.
When Angela Rasmussen, a virologist at the Center for Global Health Science and Security at Georgetown University in Washington, D.C., was a child, she received the oral polio vaccine of the inactivated virus developed by Jonas Salk in the early 1950s.
As an adult, when she had to get another dose as a condition of working in an infectious disease lab, she received a live attenuated vaccine based on research pioneered by Albert Sabin. That’s been given in the United States since 2000. “It’s not unprecedented for people to get boosters as vaccines change,” she says.
But the big difference is that by the time she received her second polio vaccination, the Sabin formulation had more than a half-century of safety data behind it.
“I don’t think we have nearly enough information that people should start mixing and matching COVID-19 vaccines,” says Rasmussen. “It’s a novel virus with a novel vaccine. We shouldn’t rush into it.”