The FDA’s new COVID-19 vaccine guidance is here. Now what?

US residents’ ability to get COVID-19 vaccines this fall is about to change as US Food and Drug Administration leaders shift away from a one-size-fits-all approach, raising concerns among vaccine researchers.

Under new guidance this week from the FDA’s top brass, annual COVID-19 boosters will be authorized only for people 65 years old and older, as well as people with certain health risks, including asthma and diabetes (N. Engl. J. Med. 2025, DOI: 10.1056/NEJMsb2506929).

US health agencies have previously recommended that everyone over 6 months old get an annual shot and that high-risk people get vaccinated every 6 months.

The change brings US COVID-19 vaccine recommendations more in line with those of several European nations, including Denmark and Switzerland. The recommendation also treats COVID-19 more like respiratory syncytial virus (RSV) than seasonal flu.

“Now we are back in line with the rest of the world,” Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees vaccines in the US, said during a webcast May 20 after the publication of the guidance.

But experts worry that instead of restoring trust in US public health—as Prasad and FDA commissioner Marty Makary say they aim to do—the change will undermine vaccination campaigns and put immunocompromised people at risk.

“It’s taking a gamble with other people’s health,” says Jonathan Howard, a neurologist and SARS-CoV-2 researcher at New York University (NYU) Langone Health who has previously criticized Makary and Prasad for their approaches to COVID-19 policy. “They’re going to end up pleasing no one because antivaxxers want these off the market, and people who want the vaccines are not going to be pleased.”

Makary and Prasad published the new guidance 2 days before a scheduled meeting of the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) and more than a month before a scheduled meeting of the US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP).

Grace Ryan, an assistant professor at UMass Chan Medical School who researches vaccine hesitancy, is concerned that the FDA appears to have skirted those committees’ processes in issuing its new guidance. “There are some, including me, who are worried about what precedent this departure sets,” Ryan says.

VRBPAC still met on Thursday, May 22, to discuss the composition of updated vaccines for the 2025–26 season. It was immediately apparent that the FDA’s announcement had caught even government officials off guard. Sarah Meyer, chief medical officer in the CDC’s National Center for Immunization and Respiratory Diseases Immunization Services Division and a member of VRBPAC, asked at the beginning of the meeting whether the new FDA framework “might affect aspects related to selecting the strain.”

“For example, if a different strain was selected for this season, would that require additional clinical trials?” Meyer asked. Jerry Weir, director of CBER’s Office of Vaccines Research and Review Center Division of Viral Products, responded that the question was “off topic.” But the same concern came up multiple times during the meeting’s public comment period.

“It is critically important to consider the practical effects of changing the vaccine target in light of the newly announced regulatory framework,” University of Wisconsin–Madison pathologist Kaitlin Sundling told the committee. “Why are two individuals making top-down decisions about vaccine policy?” she asked, adding that it sets “a dangerous and unacceptable precedent.”

Ultimately, VRBPAC focused largely on existing COVID-19 vaccines’ ability to neutralize the virus and unanimously recommended that next season’s vaccine should target the JN.1 variant.

ACIP is still slated to make recommendations during its June 25–27 meeting for what age and risk groups should be vaccinated against COVID-19.

More trials sought

For people 65 and older and people with at least one risk factor for severe outcomes from COVID-19 infection such as hospitalization, the regulatory framework stays essentially the same. But for younger people without those risk factors, the FDA is now asking for additional trials to show vaccine efficacy.

Manufacturers may have difficulty recruiting people for these trials. “One of the things Prasad did was make it seem like doing a randomized controlled trial would be as easy as snapping your fingers,” Howard says. “It will take many months or years to do.”

Pfizer spokesperson Kit Longley tells C&EN the company is “evaluating the details shared [Tuesday, May 20] and discussions with the FDA are ongoing.”

“We stand by the science behind the Pfizer-BioNTech COVID-19 vaccine and continue to believe that broad vaccination programs are an essential tool for helping to prevent COVID-19-associated hospitalizations and severe disease, including death,” the spokesperson says via email. “The Pfizer-BioNTech COVID-19 vaccines have been administered to over a billion individuals, including adults, adolescents and children, generating robust data demonstrating a favorable safety profile.”

Moderna spokesperson Kelly Cunningham likewise says in an email that the company is “committed to working with the Agency to provide the data they need to ensure access for Americans.”

Novavax, which makes the only non-mRNA vaccine available in the US, has already been through a version of this updated process. The company’s COVID-19 shot has been available in the US under an emergency use authorization since 2022 but received full approval only last week after the FDA asked Novavax to commit to a Phase 4 placebo-controlled trial in 50-to-64-year-olds without high-risk conditions, as well as additional trials assessing the vaccine’s effects on myocarditis and pericarditis. Novavax’s COVID-19 vaccine approval is limited to people who are at least 65 years old or have an underlying health condition.

Moderna, Pfizer, and other COVID-19 vaccine makers will now be subject to the same regulations. But investors and analysts are nonplussed. Share prices for Moderna and Pfizer were actually up after Makary and Prasad’s announcement.

“In our view, FDA’s updated approach to COVID vaccines is quite reasonable and could drive production of evidence to support future uptake of boosters,” Leerink Partners analyst Mani Foroohar writes in a research note.

Who can and can’t get the fall vaccine?

The list of health risks Makary and Prasad cite as reasons to warrant an annual booster is long. The list includes disorders like heart failure and Parkinson’s disease, alongside conditions such as “physical inactivity” and having a body mass index of 30 or greater.

Most people in the US would still qualify for updated COVID-19 vaccines within this framework, Prasad said during the May 20 webcast. “At-risk Americans can be reassured that they will be covered by such approvals,” he said.

But in hospitals and pharmacies across the US, it doesn’t always play out that way. It’s unclear whether health-care workers are meant to discern whether a person falls into a high-risk category or whether they can accept self-attestation. Ryan points out that many people don’t generally think of themselves as being at high risk of severe complications, even if they are.

“We believe the added barrier of proving one’s risk status will likely reduce COVID vaccine uptake this season,” Foroohar writes in his research note.

Children may also not be eligible for a shot this winter unless they are diagnosed with certain health conditions that appear on that list. That factor amounts to “taking away choice for families,” says Sean O’Leary, chair of the American Academy of Pediatrics Committee on Infectious Diseases, in a statement emailed to C&EN. “In addition, this announcement ignores the public health problem of Long COVID,” O’Leary says in the statement. “Vaccination clearly offers children and adults significant protection from post-COVID conditions.”

Up to 5.8 million children have long COVID (Pediatrics 2024, DOI: 10.1542/peds.2023-062570). So do hundreds of millions of adults (Nat. Med. 2024, DOI: 10.1038/s41591-024-03173-6). Vaccination won’t outright prevent long COVID in all instances, but it does reduce its rate and severity, Ryan says.

“We have pretty robust data that says that these vaccines probably prevent the worst outcomes of COVID. They can prevent long COVID. I haven’t seen any of these concerns raised,” she says.

Makary and Prasad do not mention long COVID in their guidance.

Health-care workers and those in close contact with immunocompromised people will also not qualify based on those statuses under the new guidelines. Early in the pandemic, when vaccines first became available, public health authorities counseled that the shots would not only protect the people that got them but also the people around them. While the shots don’t stop transmission completely, vaccination has been shown to lower viral load and duration of illness with COVID-19 across variants (J. Infect. 2024, DOI: 10.1016/j.jinf.2023.10.016).

Prasad said during his webcast that there is “no high-quality evidence that in this year, vaccinating those near an immunocompromised person provides an additional benefit for the immunocompromised person over seeking vaccines themselves.” He added that the FDA is “very interested” in such data.

Still, Ryan worries about caregivers who work with people with weakened immune systems. “If you’re working in nursing home settings or hospital settings, you’re at more risk for exposure, but also at risk of exposing people,” she says. “The language, as it stands, I think, doesn’t make these vaccines as accessible as they should be.”

NYU’s Howard agrees. “I think that any person who wants a COVID vaccine should be able to get one,” he says.