FDA is expected to authorize updated Covid-19 boosters in the coming days, but some health experts say people's varying levels of immunity may affect how protective these new boosters are.

FDA to authorize updated boosters around Labor Day

FDA is planning to authorize updated Covid-19 vaccines from Pfizer-BioNTech and Moderna around Labor Day ahead of a fall booster campaign, according to two people familiar with the situation.

The updated boosters from both companies are bivalent vaccines that target the BA.4 and BA.5 omicron subvariants, as well the as the original coronavirus strain, in one shot. Currently, BA.5 makes up almost 90% of all new Covid-19 cases in the United States, CDC data shows. By modifying the shots to match the dominant variants, health officials hope the shots will be more protective and potentially provide longer-lasting immunity.

This week, both companies finalized their applications for emergency authorization of their booster shots. Pfizer-BioNTech is seeking authorization for individuals ages 12 and older, while Moderna is seeking authorization for all adults.

However, unlike previous Covid-19 vaccines, the updated boosters have not yet been widely tested on humans. Instead, the companies submitted data on mice, as well as human neutralizing antibody data from previous studies looking at bivalent BA.1 boosters.

Some vaccine experts have argued that mice data cannot be reliably generalized to humans. But others say the country has had enough experience with Covid-19 vaccines to understand their safety and can treat them like flu vaccines, which are changed every year to match circulating strains but not routinely tested.

"We're going to use all of these data that we've learned … not only from this vaccine but decades of viral immunology to say: 'The way to be nimble is that we're going to do those animal studies," said Deepta Bhattacharya, an immunobiologist at the University of Arizona College of Medicine. "We're really not going out too far on a limb here."

In addition, Peter Marks, FDA's top vaccine regulator, said the agency has "extremely good" data from both Pfizer-BioNTech and Moderna showing that the boosters are safe and effective. "I take great issue with those who say, 'Oh, you're just approving this with mouse data,'" he said. "We're authorizing this with the totality of the evidence that we have."

CDC will have to approve the shots before they become available. Currently, CDC's Advisory Committee on Immunization Practices (ACIP) plans to meet Sept. 1 and 2 to discuss the new boosters. If CDC Director Rochelle Walensky signs off on the shots soon after ACIP's meeting, vaccinations with the updated boosters could begin as early as the day after Labor Day. 

How will the updated boosters impact immunity?

Although health officials are hopeful the updated boosters will provide greater protection against the coronavirus, some experts suggest that how well the shots work may be dependent on an individual's past exposure to the virus—whether through vaccination, infection, or both.

In a phenomenon known as original antigenic sin, people's immune systems generally carry the "imprint" of previous infections or vaccinations, which helps their bodies recognize a virus in the future. This can affect an individual's future immune response to a virus, as well as how well they respond to an updated vaccine.

"People are now walking around with different immune-imprinted covid responses, depending on what vaccine schedules they've had — one, two or three doses — and what infections they have had in the past," said Rosemary Boyton, a professor of immunology and respiratory medicine at Imperial College London. "Imprinting is different according to where you live in the world, what vaccines you received — and that's determining the subsequent immune response."

This could mean that revamped fall boosters could have limited benefits because people's first experience with the virus dominates their immune memories.

"We may have gotten about as much advantage out of the vaccine, at this point, as we can get," said Barney Graham, an architect of coronavirus vaccines who now focuses on global health equity at Morehouse School of Medicine. Still, many experts think that moving forward with updated boosters is still the best strategy.

According to the Washington Post, the impact of original antigenic sin on the coronavirus is unclear, particularly as it continues to rapidly mutate. But it could change vaccine development in the future.

"Maybe 10 to 15 years from now, we live in a world where the vaccine is birth-year specific or make strain selection decisions that take into account different immune histories in the population," said Katelyn Gostic, a researcher at the University of Chicago. "I think we need and are actively developing better technologies and better techniques to try to work at the science fiction frontier here, of figuring out these imprinting questions." (Lovelace, NBC News, 8/23; LaFraniere/Weiland, New York Times, 8/23; Johnson, Washington Post, 8/23; Twenter, Becker's Hospital Review, 8/23)