An FDA Panel Decides It’s Time For New COVID-19 Boosters

On June 28, a panel of experts convened by the U.S. Food and Drug Administration (FDA) voted 19 to 2 to change the vaccines that have been used since December 2020 to protect against COVID-19.

The change, which will apply only to booster doses for people who are already vaccinated, involves including a strain that targets the Omicron variant, which is now responsible for nearly all infections of COVID-19 in the U.S. and around the world. But the committee stopped short of deciding exactly which Omicron strain; Omicron has produced many different subvariants, starting with BA.1 and now BA.4 and BA.5, the latter two which now account for 50% of COVID-19 cases in the U.S. Including an Omicron strain in the next booster is similar to the way flu viruses are swapped out every year to give people the strongest immunity against whichever version of influenza is circulating at the time.

The committee’s decision is based on several lines of evidence, including the fact that Omicron is different from the original version of the virus in the currently approved vaccines. The original COVID-19 vaccines, as well as the booster doses that have been authorized in the U.S., have all targeted an earlier strain of the virus known as D614G, which public health experts call the ancestral strain.

The experts also heard from scientists at the U.S. Centers for Disease Control and Prevention (CDC) who provided data showing that these original vaccines are no longer as effective at protecting people from getting infected with the Omicron variant and its subvariants as they were against the ancestral strain. The vaccines continue to provide good protection against getting seriously ill with COVID-19, and from getting hospitalized or dying from the disease, but public health experts provided compelling evidence that such protection could be even stronger if the next booster shots come from a new version of the vaccine that specifically targets Omicron.

Why is a new vaccine necessary now?

The FDA committee decided that it’s time to update the COVID-19 vaccine and that continuing to boost with the existing shot will not provide the durable protection that people need. The experts reviewed data on the dominance of the Omicron variant, which has circulated in the U.S. since December 2021, and has already spawned several different subvariants, including BA.1, BA.2.12.1, BA.4, and BA.5.

The same FDA committee had met in April to discuss the criteria for changing the COVID-19 vaccine and concluded that it would take into consideration the advice of the World Health Organization’s Technical Advisory Group on COVID-19 Vaccine Composition (TAG-Co-VAC), which analyzes data on COVID-19 vaccine effectiveness and makes recommendations about when to change vaccines if that effectiveness shows signs of waning, just as a similar WHO group does for the flu vaccine each year. That group concluded in June that while the currently available vaccines made by Moderna and Pfizer-BioNTech continue to protect against severe COVID-19 disease—even if people are infected with Omicron variants—stronger immunity against Omicron could come with a booster dose with a new Omicron-containing vaccine. Dr. Kanta Subbarao, director of the WHO Collaborating Center for Reference and Research on Influenza, explained to the committee the reasoning behind the group’s advice, noting that adding an Omicron-specific component to the next booster would increase the breadth of protection people might receive from immunization. “It’s not so much matching what [virus strain] is likely to circulate, but more about achieving broader immunity [against the existing variants],” she told the committee.

Subbarao presented data showing that people who were vaccinated and then infected with Omicron generated a wider range of antibodies that could neutralize more SARS-CoV-2 variants, including the original strain and Omicron, than people who were unvaccinated and were infected with Omicron, who primarily generated immune responses specific to Omicron only.

The WHO did not, however, recommend switching to an Omicron-specific vaccine to immunize people who have not been vaccinated yet, since there isn’t data yet to support whether that immunity would be robust enough.

The FDA committee also considered several other pieces of evidence, including the fact that currently circulating versions of SARS-CoV-2, mostly from the Omicron strain, are different enough from the original virus that the vaccines target, and that available vaccines are less effective in protecting against Omicron infections than they are in protecting against other variants. The committee reviewed data showing that while the current vaccines continue to protect against severe disease, the level of virus-fighting antibodies in vaccinated people, including those who have received a booster shot, wanes over time.

Taking into account all of the available data, the FDA panel decided that there was enough evidence to justify changing the COVID-19 vaccine booster to better target the Omicron variant currently responsible for nearly all infections.

Which version of Omicron will the next vaccine target?

This question led to the most division among the invited speakers and the committee members. While Subbarao from WHO suggested including BA.1 in the next vaccine, because of its genetic difference from the original SARS-CoV-2 strain in current vaccines, Dr. Peter Marks from the FDA disagreed, preferring instead to focus on BA.4 and BA.5. “The current vaccines appear to be the least effective against them,” he said.

Both Moderna and Pfizer-BioNTech provided data on new vaccines they developed that contain two strains of SARS-CoV-2: the original, and one that targets the first Omicron variant, BA.1, in so-called bivalent vaccines. This approach is similar to that used in the flu shot, which typically targets three different influenza strains.

The companies also developed and studied vaccines aimed at just the BA.1 Omicron variant, but found that combining the Omicron and original strains provided a broader immune response against more than just the Omicron strain.

The committee was not tasked with deciding which version of Omicron should be included in the new booster shot, although the committee members leaned toward targeting BA.4 and BA.5, since those are increasing in prevalence in the U.S. But there is little data involving the efficacy of BA.4 and BA.5-containing vaccines, and the committee members urged the companies to continue studying those versions, which both Moderna and Pfizer-BioNTech are doing.

Will the new vaccine provide better protection against Omicron?

That’s the hope, although there is still limited data from the real world on how much stronger the protection against Omicron will actually be. The companies tested their bivalent vaccines for their ability to produce virus-fighting antibodies, in the lab, against Omicron, and the committee extrapolated from those studies that the level of antibodies would be sufficient to provide protection against infection and disease.

It’s not clear whether people vaccinated with the bivalent vaccine targeting BA.1 will produce the same levels of antibodies against the newer Omicron subvariants, including BA.4 and BA.5, as against BA.1. Moderna is studying how the immune response to BA.4 and BA.5 generated by its BA.1 bivalent vaccine compares to that against BA.1, and Pfizer-BioNTech provided early data from a mouse study. That data showed that its bivalent vaccine did produce antibodies against BA.4 and BA.5 strains, albeit at lower levels than against BA.1 or the original virus strain. Both companies are continuing to study their new vaccines against the newer Omicron subvariants that will likely become more prevalent in coming months.

Are the vaccines safe?

Some committee members raised questions about whether the bivalent vaccines, which would target two different SARS-CoV-2 strains, would generate more side effects, including myocarditis, an inflammation of heart tissues that affects mostly adolescent males. In short-term data provided by Moderna and Pfizer-BioNTech and reviewed by the FDA, side effects and adverse reactions to the new vaccines measured about one months after vaccination occurred at similar rates as those to the original doses, but longer term follow-up is needed.

Will other new vaccines come later this year?

The committee also saw data from Novavax, which makes a COVID-19 vaccine using a different technology from the mRNA platform behind Moderna and Pfizer-BioNTech’s vaccines. The FDA is still reviewing the company’s request for emergency use authorization and has not yet made a decision. But many committee members were impressed with the data from the Novavax’s original vaccine candidate, which targets the original SARS-CoV-2 strain but generated strong immune responses to a variety of variants, including against Omicron. Dr. Glenn Gregory, the company’s president of research and development, argued that the data made a good case for deploying Novavax’s vaccine, with at two doses, to better fight the current Omicron cases. But because that vaccine isn’t authorized, and the data haven’t been reviewed by the FDA yet, it’s not clear how valid that evidence is.

When could the new booster doses be available?

Both Moderna and Pfizer-BioNTech have begun manufacturing bivalent vaccines aimed at BA.1, and Moderna said if the U.S. government decided to boost with that shot, it could have hundreds of millions of doses available by July or August.

If regulators decide on a bivalent vaccine containing BA.4 or BA.5 strains, however, both companies would need about three months to manufacture those shots and go through FDA review, so those vaccines would not be available until October or November if the FDA and CDC authorizes them.

Now that the FDA’s advisory committee recommends including some version of Omicron in the next booster shot, it’s up to the FDA to review the available data, or ask for additional data from the vaccine makers, to decide which Omicron strains to include and when people should be boosted. The panel’s decision is only the first in a long series of steps—and more studies—that are required before anyone receives a new COVID-19 vaccine in the fall. “What I’d like to see are additional data, and better understanding of the clinical meaningfulness on the impact on severe outcomes and disease,” said Adam Berger, director of clinical and healthcare research policy at the National Institutes of Health. “I’d like further data on the long-term durability of any type of change to the actual vaccine composition.”