Experts say the coronavirus is likely to continue mutating, leading to additional new variants. So, will annual booster shots of Covid-19 vaccines be necessary? Some experts say they might be, but others think it's too soon to tell.

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Will 1 or 2 booster shots be enough?

Ali Ellebedy, an associate professor of pathology and immunology at Washington University School of Medicine, said he has found that, six months after a second dose of an mRNA vaccine, immune response is still maturing.

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"There is an ongoing reaction in our lymph nodes that's going for six months," Ellebedy said. "And that reaction, we are showing, that it is actually enhancing the potency of the antibodies. Even before the third dose."

That maturation would be accelerated by a third dose and could lead antibodies to improve through a process called affinity maturation, in which the antibodies get better at recognizing their target, even if the virus changes, STAT News reports.

"If you wait six months or more between a priming and boost, what you see is not just a boosting of the immunity that you got from the first vaccine, but you see a broadening of the immune response so that it recognizes other viruses or other variants," said David Topham, an immunologist at the University of Rochester Medical Center and director of the New York Influenza Center of Excellence. "Your immune response becomes much more cross-protective."

Barney Graham, an immunologist and former deputy director of NIH's Vaccine Research Center, said he's found in his research that antibodies induced by delayed booster shots are higher quality and generate a broader immune response that's better at recognizing mutated viruses.

"Once you give the [antibody-producing] B cells a chance to mature and then boost them later … that type of response tends to make immunity across all these different variants more similar," he said.

"So I think that the whole question about durability of immunity is going to have to be determined by three years from now, are people still getting sick or are they relatively well-protected against severe disease—regardless of whatever their antibody level is in serum," Graham said. "Because that may wane, but you still have a lot of memory B cells that can rapidly respond."

Marion Pepper, a researcher at the University of Washington, said based on what her team of researchers has seen, she expects boosters will give "an important window of enhanced protection," but doesn't believe the benefits of getting a booster shot over and over are limitless.

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"I think there is a misconception that the immune system can constantly be repetitively elevated such that you don't go back to that same starting point," she said. "And in some people, maybe if they didn’t have a good first immune response, it will enhance their cell numbers. But for the large majority you end up hitting a set point of memory that doesn’t just keep getting bigger every single time you get the same boost."

Or will annual booster shots like the flu vaccine be necessary?

Meanwhile, other experts argue that, similar to the annual flu vaccine, new Covid-19 booster shots will be needed every year.

Paul Bieniasz, head of the laboratory of retrovirology at Rockefeller University, said he had hoped booster shots would help people gain an upper hand against the virus. But the rise of the omicron variant has led him to believe our immune systems may not be able to lead in "a genetic arms race."

"I was much more confident a couple of weeks ago that the antibodies would have the edge in being able to outstrip the evolutionary capacity of SARS-CoV-2," Bieniasz said. "But I don't think that's completely clear now."

Gabor Kelen, professor and chair of the department of emergency medicine at Johns Hopkins University, said we'll likely have to deal with some form of the coronavirus for the rest of our lives, with variants "swirling around." But whether that means annual boosters will be necessary remains to be seen, he added.

Will people be willing to get indefinite mRNA booster shots?

While policymakers debate the need for repeated booster shots, some public health experts worry that people may not be willing to get annual boosters—even if they are helpful.

As immunity against Covid-19 continues to increase, Ellebedy said, "People in a pandemic can accept things, but I think if you're talking about a regular vaccine that's not really needed because of a pandemic, I'm not sure if people would be more accepting of that."

Additionally, Ellebedy doesn't think people will be willing to deal with the potential side effects of the current vaccines every year. John Wherry, director of the Institute for Immunology at the University of Pennsylvania, agreed, suggesting people will likely be drawn to other types of vaccines as boosters down the road, if we need them.

Akiko Iwasaki, an immunologist at Yale University, said she believes Covid-19 vaccines that are administered differently will be necessary if we want to prevent future infections.

"Early data from Israel is showing that the third dose, even though it provides a very effective protection, it also does wane," Iwasaki said. "So it's not like the third dose will fix antibody response forever. That's kind of hard to ask any vaccine to do that."

Iwasaki said developing a vaccine that provides immune protection to the mucosal tissues of the upper respiratory tract would be able to stop the coronavirus right where it enters the body, rather than letting it run through our cells. "It's really like putting the guard outside the door as opposed to inside the door," she said. (Branswell, STAT News, 12/15; Jacoby, TODAY, 12/13; Agustin, Insider, 12/12)