6 big questions about new Omicron-targeting boosters answered

For the first time since the COVID-19 vaccines rolled out in December 2020, we have updated shots that match the primary variants in circulation. Unlike the original vaccine, which targets the ancestral virus strain, the new boosters specifically target Omicron BA.4 and BA.5, which are now dominant in the United States and responsible for most new COVID-19 cases across the country.

On August 31, the U.S. Food and Drug Administration authorized the use of these updated boosters and the Centers for Disease Control and Prevention endorsed them on September 1. These decisions have come as immunity conferred by prior vaccination or infection is waning against these highly contagious versions of Omicron. Scientists are predicting an increase in COVID-19 infections in the fall and winter.

Giving the original COVID-19 shot as a second or third booster would probably help increase antibody levels against the virus, said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, at an August 31 virtual news conference. But the idea with the updated vaccine is also to achieve a longer duration of protection. It will take several months before researchers can collect the data and determine whether this will happen. No matter how incremental the benefits are from the reformulated shot, Marks said, “It’s really important for people to think about getting boosted.”

Here’s what we know so far about the new vaccines now available across America—including why they’re necessary, who can get them, and how long they are expected to protect against COVID-19.

1. What exactly is the new booster?

Unlike the original COVID-19 vaccine, the updated version is bivalent, meaning it has two mRNA components—one from the ancestral SARS-CoV-2 virus and an additional one that is common to both BA.4 and BA.5.

“It is matched to what is currently circulating,” Marks explained. “The hope here is by increasing the amount of antibodies we have to that particular variant, we’ll restore the kind of protection that we had when we first saw these vaccines launched in late 2020, early 2021.”

The goal with these modified boosters is to curtail COVID-19 hospitalizations and deaths linked to BA.4 and BA.5 or similar variants as we spend more time indoors in the fall and winter.

2. Why did we need updated shots? 

As Omicron BA.1 arrived in late November last year, it spurred a surge in COVID-19 cases. Even among those fully vaccinated, breakthrough infections were on the rise as the new variant evaded immunity conferred by the shots or a prior infection. As the virus evolved to the more transmissible and more immune-evading Omicron subvariants BA.4 and BA.5, reinfections and breakthroughs emerged even among those who were boosted. Although the shots still did a good job of protecting people from severe disease, they weren’t as effective at fending off infections induced by these new forms of Omicron.

Because the BA.4 and BA.5 spike protein sequence shares many similarities with the ancestral SARS-CoV-2 spike, the old boosters can still generate antibodies against these subvariants—but their effects are limited: In a July 7 New England Journal of Medicine paper, researchers found that in 27 fully vaccinated and boosted participants between the ages of 23 and 76, antibody levels were highest against the ancestral virus strain and 20-fold lower against BA.4 and BA.5 two weeks after receiving the old booster.

What’s unclear is how antibody numbers translate to the effectiveness of the vaccine, another study found that antibody levels waned substantially within three months of the boost. Both studies indicate that original vaccine recipe isn’t a good match for BA.5.

3. Who can get the updated shots? 

For now, individuals 12 years of age and older are eligible to get their bivalent booster provided it’s been at least two months since they last received a COVID-19 shot. For people who’ve had a recent COVID-19 infection, the CDC recommends waiting for three months from the date symptoms first appeared or the date of a positive test result.

The FDA has authorized the use of the new Pfizer-BioNTech COVID-19 boosters in individuals 12 years of age and older. Moderna’s new booster dose can be used by people ages 18 and older. With these authorizations, the FDA has suspended the use of previous boosters produced by these companies in people older than 12 years.

With flu season on the horizon, people might consider getting flu shots along with the COVID-19 boosters, but the CDC recommends young adult males who’ve received a monkeypox vaccine wait four weeks until they get their COVID-19 jab. This is mainly due to an unknown risk of rare heart conditions arising from taking the Jynneos monkeypox vaccine.

4. Will we need new boosters again soon?

The durability of protection conferred by these updated vaccines remains unknown. “That’s the million-dollar question—how long will immunity last,” says Kanta Subbarao, director of the World Health Organization's technical vaccine committee. “We still don’t understand what we need to do to elicit durability.”

While the bivalent vaccines may provide better protection against BA.4 and BA.5, they haven’t been designed to prevent virus transmission or infections, she says. And how long they’ll continue to provide protection will also depend on what the next variant might look like and how good it is at evading immune cells.

“At this point, we’re vaccinating everybody because we want to reduce the burden of disease and transmission,” Subbarao says. But the aspiration of the next generation of COVID-19 vaccines, which are in the making, will be to reduce breakthrough infections.

5. The U.S. and the U.K. are using different bivalent vaccines. Does it matter which shot you get?

The U.S. FDA picked BA.4 and BA.5 for the new vaccines because they’re currently circulating in America and many other parts of the world—unlike BA.1. Based on recent studies, Marks and his FDA colleagues think that targeting BA.4 and BA.5 may also provide more robust protection against several past COVID-19 variants including BA.1, Delta, and Beta.

The United Kingdom, on the other hand, has authorized the use of bivalent vaccines containing the ancestral strain and the original BA.1 strain. It’s possible the country may switch to shots that also include BA.4 and BA.5.

But Subbarao argues that either of the bivalent vaccines should provide a greater immunity.

6. What we know and don’t we know about these boosters?

The FDA authorized the use of BA.4/5-targeting bivalent vaccines based on limited data.

They relied on experiments Moderna and Pfizer-BioNTech conducted in mice, which showed higher antibody levels against BA.4 and BA.5 using the new booster versus the original formulation. They also looked at the results of human clinical trials using a version of the vaccine with BA.1, which showed that the bivalent booster generated higher levels of antibodies against Omicron and all SARS-CoV-2 variants than the original vaccine.

The expectation is that BA.4/5 bivalent boosters will perform better.

“What we don’t know is … how well this is going to work in the real world,” says John Swartzberg, an infectious disease expert at the University of California, Berkeley. Also, to what extent these modified shots will reduce reinfections and breakthrough ones remains unknown.

Other experts like Pablo Sanchez, a pediatrics professor at Ohio State University, have questioned the decision to go forward with the new COVID-19 shots without relevant data from human trials. He was the only one to vote against recommending the updated shots in the CDC meeting.

The process mirrors how annual changes are made to the influenza vaccine, which doesn’t require human clinical trials to assess its safety and efficacy, but Sanchez says, “I didn’t think we are there with COVID vaccines.” He is 67 and will get a bivalent booster, but Sanchez says he would have felt more comfortable recommending the shot if he could confidently say it’s safe rather than likely to be safe.

Swartzberg, on the other hand, isn’t too concerned. “It has a piece of the ancestral strain component in it,” he says. At worst, it will be like using the original vaccine to boost again, he says.

Waiting for the proof, however, would have meant that a fall or winter COVID-19 wave could have arrived without updated vaccines, said FDA commissioner Robert Califf at the news conference. Both Modera and Pfizer-BioNTech are now conducting human clinical trials to test the safety and efficacy of the modified boosters, but Califf encourages those eligible to get their shots soon.