Only Include Omicron in Next COVID Vaccine, Says FDA Panel

An FDA advisory panel unanimously recommended that COVID-19 vaccines for the fall be updated to only include Omicron XBB lineages.

On Thursday, all 21 members of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) agreed that excluding the ancestral strain is the best path going forward, though some stressed that could change in future years.

"We no longer need the Wuhan strain," said Amanda Cohn, MD, of the CDC in Atlanta. "I do want to be careful that we're clear that for this update it's monovalent. It may not be monovalent in future updates."

XBB lineages are "antigenically distinct" from prior Omicron subvariants, noted panelist Michael Nelson, MD, PhD, of the UVA School of Medicine in Charlottesville, Virginia. Furthermore, he said, data show the current vaccines are losing efficacy against these strains, which currently account for 95% of COVID cases worldwide.

"We now have data supporting better efficacy with the candidate vaccines under discussion," Nelson said. "It does make perfect sense to move toward a monovalent vaccine, but whether that holds up for future years, I don't think we know at this point."

The FDA appears poised to recommend that manufacturers Pfizer, Moderna, and Novavax all target XBB.1.5 with their 2023-2024 vaccines. Currently the leading U.S. strain, XBB.1.5 is responsible for 40% of cases.

XBB.1.5 appears to be "at the front of the line," said Peter Marks, MD, PhD, director of the FDA's Center for Biologics Evaluation and Research, noting that the data on the vaccine candidates targeting this strain have shown very good neutralization across XBB variants.

The agency asked VRBPAC to weigh in on whether they had a preference for XBB.1.5, or two emerging strains -- XBB.1.16 and XBB.2.3 -- which together comprise roughly 25% of U.S. cases, but panelists generally took no issue with the FDA's plan.

"We're in a different situation than we were last time when we were talking about BA.1 versus BA.4/5, where we actually had some data that suggested that BA.4/5 may be a better choice," said Steven Pergam, MD, MPH, an infectious disease specialist at the Fred Hutchinson Cancer Center in Seattle. "I don't think it seems as though the XBB viruses are that much different."

Stanley Perlman, MD, PhD, of the University of Iowa agreed, adding that it likely wouldn't matter if XBB.1.16 or XBB.2.3 were to become dominant. "I think we have good data that there is really good cross reactivity."

Among the considerations for the switch to a monovalent product was concern around immune imprinting, a phenomenon whereby the immune system is primed to respond to the ancestral strain of SARS-CoV-2 given the multiple exposures with the initial two-dose vaccine series and subsequent boosters.

"I do think that taking out the ancestral strain will do something to optimize the response simply because you won't be competing with something that people have already seen two, three, four times," Jerry Weir, PhD, director of the Division of Viral Products at FDA, told the committee.

Some evidence has suggested that the currently available bivalent vaccines may have been less effective against the intended targets -- Omicron BA.4/5 -- due to immune imprinting.

And during the meeting on Thursday, industry representatives showed lab data suggesting that monovalent XBB compositions more effectively neutralized currently circulating strains than bivalent compositions.

Some members expressed unease that COVID vaccines would follow the flu shot schedule in being updated each year, or "season."

Using the word "season" is problematic, said Mark Sawyer, MD, of the University of California San Diego. "It links the campaign to the influenza vaccine, and I understand that it may be convenient and most efficient to give the vaccines together, but you know it's only been a few years. We don't really know what the COVID season is."

"It may ultimately confuse people about when and where they should get vaccinated and how frequently," Sawyer added.

Not everyone will need a shot every year, said committee member Paul Offit, MD, of Children's Hospital of Philadelphia.

"I agree with [the FDA] assessment that it is those highest risk groups that may benefit from a booster dose," he said. "We need to continue to define who those high-risk groups are and not make this a recommendation for everybody, every season."

Offit noted that evidence of T-cell immunity against COVID should not be ignored either when considering updates. It's a problem if the influenza vaccine strain is "missed by a mile," but that's not true with COVID as "T-cell recognition sites remain conserved," he said.

While the FDA is not required to follow the recommendations of its advisory committees, it typically does.

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