F.D.A. Says Next Covid Boosters Should Target Omicron Subvariants

WASHINGTON — The Food and Drug Administration said on Thursday that it had advised coronavirus vaccine manufacturers to update their booster formulations to target the fast-spreading Omicron subvariants known as BA.4 and BA.5, which are now estimated to account for more than half of new virus cases in the United States.

The decision came just two days after the agency’s committee of independent vaccine experts overwhelmingly voted for regulators to adopt more advanced vaccines tailored to forms of Omicron, an acknowledgment that the current shots may no longer be as protective for at least some Americans by the time a possible fall or winter surge arrives.

“As we move into the fall and winter, it is critical that we have safe and effective vaccine boosters that can provide protection against circulating and emerging variants,” Dr. Peter Marks, who oversees the F.D.A.’s vaccines office, said in a statement Thursday.

Dr. Marks said the agency was not asking Pfizer-BioNTech and Moderna to change the formulation for initial doses of their coronavirus vaccines, since the current makeup “provides a base of protection against serious outcomes.”

Instead, he said, “We expect this coming year to be a transitional period when this modified booster vaccine may be introduced.”

The decision to take aim at the BA.4 and BA.5 subvariants of Omicron, arguably the most transmissible forms of the coronavirus to date, comes despite considerable uncertainty around what the virus will look like later this year, making the design of fall booster shots uneasy guesswork for the manufacturers and the federal scientists charged with guiding them on how to retool their products.

The agency recommended that manufacturers produce a so-called bivalent vaccine targeting BA.4 and BA.5 along with the original coronavirus, believing that a match between current variants and the updated booster could provide stronger and more durable protection against whatever is in greater circulation months from now. Some of the agency’s advisers said this week that such a formulation could possibly broaden immune responses more than a shot aimed only at Omicron.

The current makeup of shots still appears to offer substantial protection against severe outcomes from Covid-19. Many Americans have also been infected with Omicron or its subvariants. Hospitalizations and deaths have increased modestly as the Omicron subvariants have grown dominant, but they remain far lower than at the height of the winter Omicron wave.

But the F.D.A. has said that the risk of another major outbreak will rise later this year “due to the combination of waning immunity, further evolution of variants and increased indoor activity.”

Pfizer and Moderna are expected to accept the F.D.A. recommendation and start producing reformulated doses this summer, looking to have them ready by fall if federal regulators authorize them for a new booster campaign. Before the expert committee’s vote on Tuesday, Pfizer said that a shot aimed at the chosen subvariants could be ready for use in early October, while Moderna has projected availability by late October or early November.

Billions of dollars are at stake. The Department of Health and Human Services on Wednesday said it had made an advance purchase of 105 million doses of Pfizer-BioNTech’s vaccine for $3.2 billion, timed for possible fall deployment, with options to buy up to 300 million doses. Xavier Becerra, the health secretary, called the contract “an important first step to preparing us for the fall.”

The Biden administration, which has warned that it is low on funds for its pandemic response, used repurposed money to buy the vaccines, betting on a next generation of boosters without knowing who might need one or how they will perform.

Officials at the F.D.A. have said that in order to have an option ready by the fall, the design of the vaccine would have to be selected by early summer, or else manufacturers would not have enough lead time. Experts advising them, including Centers for Disease Control and Prevention officials, agreed with that urgency at the Tuesday meeting, with many recommending the bivalent option aimed partly at Omicron subvariants.

Dr. Ofer Levy, the director of the precision vaccines program at Boston Children’s Hospital and an adviser to the F.D.A., said he supported the Thursday recommendation. “F.D.A. is in a tough spot,” he said. While regulators could benefit from more data, he added, “we also have to make a damn decision here because the fall is coming.”

Dr. Marks, in his Thursday statement, said that research had shown protection from initial doses and boosters waning against variants, including Omicron. He suggested earlier this week that at least older Americans, who died at greater rates during the Omicron wave, might need the additional shot — a point that even F.D.A. advisers skeptical of a wide-ranging fall booster campaign agree on.

But federal health officials have not yet determined who might be eligible come October, or how protective the updated shots might be.

Dr. Paul A. Offit, an F.D.A. panelist and vaccine expert at Children’s Hospital of Philadelphia, said that federal regulators had not shared data for either an Omicron- or subvariant-targeting bivalent vaccine that proves either “clinically significantly increases your chance of being protected against severe disease.”

Further complicating the task for regulators and their advisers this week were contrasting Moderna and Pfizer-BioNTech studies on vaccines targeting Omicron, with results that some experts said were underwhelming. Moderna had hoped to produce a bivalent vaccine that combined Omicron and the original coronavirus vaccine, known as the prototype. Pfizer and BioNTech delivered better results from a shot aimed only at Omicron.

A Pfizer official said this week that preliminary data from a mouse trial showed that a vaccine targeting BA.4 and BA.5 could elicit a strong immune response but that researchers did not yet have a side-by-side comparison with a booster aimed at the earlier form of Omicron.

The companies found that vaccines targeting Omicron induced higher levels of antibodies against the variant than the existing vaccines, but with a relatively modest increase.

Dr. Levy, the advisory committee member, said there were still encouraging takeaways from the company data, including that the new booster candidates appeared safe, as well as hints of durability. He compared the F.D.A. recommendation to the decisions scientists must make each year in selecting influenza strains with the hope that they will match what is in circulation later in the year.

Some vaccine experts were still miffed at the F.D.A.’s push for the Omicron booster update.

“Moderna and Pfizer executives have claimed that the Omicron vaccines will be protective for longer. That may be true, but how long is longer? A few weeks? A month or two?” Drs. Offit and John P. Moore, another vaccine specialist, wrote in a column this week in Stat. “It’s important to be sure that changing the booster vaccine to include the Omicron sequence offers enough of an advantage to justify the cost and complexity associated with making the switch.”

Dr. Moore, a virologist at Weill Cornell Medicine, said on Thursday that the decision to update the booster to address BA.4 and BA.5 without robust data could in part be attributed to pressures the Biden administration may face to appear prepared for another wave of virus cases.

“Including an Omicron vaccine component is a politically safe decision that would be less criticized than making no change,” he said. “There’s a middle ground between the need for nimbleness and the desirability of thoroughness. F.D.A. did not find it.”

Sharon LaFraniere contributed reporting.