FDA Experts Vote to Make All COVID-19 Vaccines and Boosters Bivalent

In a unanimous decision, all 21 voting members of the U.S. Food and Drug Administration’s (FDA) vaccine committee recommended that the U.S. start using the same COVID-19 virus strain in all of the COVID-19 vaccines, including primary and booster doses.

That means the bivalent booster dose, which targets both the original SARS-CoV-2 strain and the Omicron BA.4/5 strains, would soon become the only type used for all primary shots and boosters.

The decision reflects a turning point in the pandemic. Until now, vaccine makers have tried to keep up with constantly evolving variants, but they’ve always been a few steps behind. The variants targeted in the bivalent booster, for instance—which the FDA only authorized in September—have since been eclipsed by the newer Omicron variants BQ.1.1, XBB.1, and XBB.1.5. Standardizing all vaccines to target the same strains—then evaluating whether they should be updated on a regular cadence, an approach the committee seemed enthusiastic about—would make variant-chasing a thing of the past.

The committee heard data from FDA scientists, scientists at the U.S. Centers for Disease Control and Prevention (CDC), and vaccine makers. The research they presented all suggests that the bivalent booster generates stronger (albeit not dramatically higher) levels of antibodies against even the latest virus variants.

The data included early looks at how the bivalent booster protected against the latest variants BQ.1.1, XBB.1, and SBB.1.5. Moderna and Pfizer-BioNTech showed that the bivalent boosters still provided some protection against these new variants, in the form of antibodies that were several fold higher than levels generated by the original vaccine when used as a booster. Antibodies are the first line of immune defense, and are primarily focused on blocking the virus from infecting cells. Citing previously reported data, Moderna showed that its bivalent booster generated levels of antibodies to neutralize the BQ.1.1 and XBB.1 that were several times higher than those produced by the original vaccine, while Pfizer-BioNTech referenced a recently published study in the New England Journal of Medicine showing responses of a similar magnitude.

This data, plus the appeal of a simpler immunization regimen, persuaded the panel. “Simpler is better, and we saw evidence today that closer is better,” said committee member Dr. Michael Nelson, professor of medicine at University of Virginia, referring to the fact that the BA.4/5 in the bivalent vaccine is a closer match to the currently circulating Omicron variants than the virus in the original vaccine. “I’m hoping that the momentum for simplification, along with the efficacy and safety data, spurs additional vaccination and acceptance of these vaccines in all age groups.”

Dr. Ofer Levy, director of the precision vaccines program at Boston Children’s Hospital and member of the committee, agreed. “As we turn the corner from the pandemic to endemic phase, today’s vote marks a big practical win for the American people,” he said. “It’s going to really simplify things and benefit public health.”

Lingering questions

The experts noted that there are still gaps in what health officials know about how the bivalent vaccine is providing immunity. Data presented at the meeting showed that the additional benefit in protecting against infection is still short-lived, while the protection from the original vaccines in keeping people from getting severely ill appears to be more durable. At future meetings, the committee will consider whether to continue including the original SARS-CoV-2 virus in future immunizations, in so-called multivalent shots, or whether vaccines should contain multiple new variants that better match whatever new forms the virus might take.

The committee discussed, but was not tasked to resolve, other issues. The most notable were about whether to move to an annual COVID-19 booster schedule and conduct yearly reviews each June to better match vaccines to whatever version of the coronavirus will likely be circulating the following winter. (The U.S. takes this approach with influenza shots.) The committee members were in favor of these strategies and will make more concrete decisions about them at a meeting in June. Those decisions also require coordination with global health bodies, including the World Health Organization (WHO), to sync immunization strategies to ensure that vaccines are targeting the viruses that are causing the most health issues.

Novavax, which makes a COVID-19 vaccine authorized for use as both primary immunization and a booster in the U.S., also presented data at the meeting. Its shot uses a different technology based on a recombinant form of the spike protein on the SARS-CoV-2 virus, along with an adjuvant to wake up the immune system. Novavax reported that its vaccine generated similar protection as that of the mRNA bivalent boosters. Based on that data, the company argued that because its technology targets more conserved portions of the viral spike protein, it could generate broader protection that might include even future variants of SARS-CoV-2. However, Novavax added that it would take about six months to update its vaccine with any new variant targets, while the mRNA manufacturers estimated that it would take roughly half that time to update theirs.

The experts also raised questions about some cases of stroke that CDC scientists are continuing to investigate to determine if the bivalent vaccine raises risk of these events. “The evidence is not sufficient to conclude a safety problem with respect to stroke,” said Dr. Tom Shimabukuro, deputy director of the H1N1 vaccine task force in the immunization safety office at the CDC. “The CDC recommendations are that everyone who is eligible should get a bivalent booster. We’ll continue to do more work on this, through more formal epidemiological investigations, and make the information available as it becomes known to us.”

Next steps

Today’s vote to make all COVID-19 vaccines the same bivalent formulation did not specify a date by which this should happen. But the FDA will now take the committee’s advice under consideration as it formulates a revised vaccination plan for COVID-19, including whether to move to a yearly or more regular immunization schedule, and which strains to include. “I’m curious about the next stage of discussions involving choosing the [virus] strain,” said Dr. Steven Pergam, medical director of infection prevention at the Seattle Cancer Care Alliance and a member of the committee. “That’s where the rubber meets the road.”