FDA advisers say new shots can target more recent SARS-CoV-2 variants

SARS-CoV-2 keeps evolving, and it’s time for COVID-19 vaccines to again follow suit, advisers to the U.S. Food and Drug Administration (FDA) agreed today. The panel voted unanimously in favor of updating the shots to more closely match virus strains now circulating. Although FDA still needs to greenlight the change, the next iteration of vaccine is likely to match one of two versions of the virus, either JN.1, which emerged in September 2023, or one of its descendants, such as KP.2 (colloquially known as a “FLiRT” variant). Although such offshoots are now circulating more widely than JN.1, advisers urged FDA to at a minimum permit JN.1 vaccines, because the company Novavax is already working on one and says it can’t quickly pivot to something different.

A retooled vaccine, it’s hoped, will be more likely to blunt COVID-19 symptoms and the risk of hospitalization, and somewhat dent transmission of the virus compared with the current version, which is tailored to XBB.1. That strain has now vanished, and 94% of infections are attributed to the JN.1 family. In late April, the World Health Organization (WHO) asked vaccine companies to supply JN.1 vaccines globally later this year.

The advisory committee considered whether FDA should follow WHO’s lead, embracing JN.1, or request a vaccine containing one of its progeny, some of which are now circulating much more widely than their parent. All three companies supplying COVID-19 vaccines to the United States—Moderna, Pfizer, and Novavax—said at the meeting they can have ample supply of a JN.1 vaccine available by late summer. But Novavax followed the WHO recommendation and has already settled on a JN.1 vaccine because its protein-based product requires roughly 6 months to produce, longer than messenger RNA (mRNA)-based vaccines from Moderna and Pfizer. Novavax Chief Medical Officer Robert Walker says the company could not offer a fall vaccine in the U.S. if FDA requested a different strain, such as KP.2.

The committee’s recommendation to keep JN.1 on the table would preserve the current mix of vaccine options. Peter Marks, director of FDA’s Center for Biologics Evaluation and Research, noted the agency could still ask Pfizer and Moderna to include a different strain. That’s the advantage of mRNA technology, he said, “to have the freshest vaccines.”

Although the advisory committee’s 16-0 vote to update the vaccine was no surprise—researchers are now attuned to SARS-CoV-2’s shape shifting—unanswered questions kept bubbling up. It’s still unclear whether and to what degree young, healthy people benefit from annual COVID-19 vaccinations, whether regular boosting cuts the risk of Long Covid, and how long protection from severe disease after vaccination lasts.

Data presented at today’s meeting by Ruth Link-Gelles, an epidemiologist at the U.S. Centers for Disease Control and Prevention (CDC) indicated protection from symptoms and hospitalization took a nosedive within 6 months of an updated XBB shot—sometimes to near zero. Earlier publications have reported a similar waning of COVID-19 vaccines. But protection against death and intensive care unit admission was much more durable.

The endless permutations in the number of vaccine doses and the number and timing of infections in the U.S. population are making it harder to resolve some questions about the shots. Still, many “are answerable, but I don’t know if people are interested in answering them by collecting the data,” says David Ho, a virologist at Columbia University who posted a preprint last month analyzing recent SARS-CoV-2 evolution and how different variants might respond to vaccination. “The pandemic is gone in most people’s minds.” That was reflected by last year’s vaccine uptake: Just 22% of adults in the U.S. got a COVID-19 vaccine, compared with 48% who rolled up their sleeves for a flu shot.

The sluggish numbers may also reflect confusion about who needs an annual COVID-19 shot. Last year, U.S regulators recommended a fall dose for nearly everybody. But many countries in Europe now restrict annual doses to older people, health care workers, and those with risk factors such as a suppressed immune system, in part because of uncertainty about whether the benefits of a yearly shot for all outweigh any risk of side effects.

“We haven’t any data to really decide on when a healthy individual would need to be boosted again,” says Klaus Überla, a virologist at the University of Erlangen-Nuremberg and chair of the Standing Committee on Vaccination, which crafts national vaccine recommendations. German officials are tracking vaccine research worldwide and monitoring SARS-CoV-2 virus levels in local wastewater and rates of severe disease to help them decide whether and when to open revaccination to healthy people under age 60.

Another urgent question is whether COVID-19 vaccines slice risk of chronic post–COVID-19 conditions. A study published last month in Nature Communications by a team at Kaiser Permanente found vaccination reduced risk of various Long Covid symptoms by 10%. But the roughly 300,000 people included in that study were infected in 2021 or early 2022. “I’m not aware of recent data from this current vaccine,” Link-Gelles told the committee. The power of COVID-19 vaccines against Long Covid “is particularly difficult to study.”

Both Pfizer and Moderna presented mouse data at the meeting showing that JN.1 and KP.2 vaccines performed roughly comparably against current strains. That leaves researchers guessing about their relative advantages in people. “Does it matter” if one vaccine version produces slightly higher blood antibodies to neutralize one virus than another, wonders Kirsten Lyke, an infectious disease specialist at the University of Maryland School of Medicine, who was not part of the committee but has studied the vaccines—or are “all of these kind of OK?”

Given SARS-CoV-2’s unpredictability, “having a vaccine that’s the trunk of the tree”—the JN.1 parent—“rather than the branches makes sense to me,” said committee member Archana Chatterjee, a pediatric infectious disease specialist at Chicago Medical School.

After FDA makes an official determination on the fall vaccine makeup, CDC’s Advisory Committee on Immunization Practices will meet later this month to discuss recommendations about who should get the shot.