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FDA advisers grapple with how to update COVID-19 vaccines

A group of advisers to the Food and Drug Administration agreed Wednesday that COVID-19 vaccines will likely need to be updated to keep pace with a fast-changing coronavirus, but said they would need more information to guide future decisions.

The FDA convened the group, made up of independent vaccine and public health experts, to provide input on how drugmakers should adapt their vaccines to better guard against variants like omicron, or others that might emerge over time.

The question is an urgent one, as roughly half of U.S. adults who received a two-dose vaccine series have yet to get a third dose, which has been shown to restore some protection and boost waning antibody levels. The FDA authorized booster doses for all adults in November and last month cleared a fourth dose for older adults and people who are immunocompromised.

“Coming into the fall season, only half of the population overall has received a third dose,” meaning the other half won’t have durable protection, said Peter Marks, head of the FDA office that reviews vaccines, at Wednesday’s meeting.

“That’s a lot of vaccine,” he added. “Do you modify your vaccine composition so that, when you do boost those people, you give them the best chance of having longer-lasting protection?”

Experts on the panel attempted to answer that question, but struggled with how to determine the best composition and to assess whether it remained sufficiently safe and effective for broad use.

“We’re looking at a conundrum here,” said Ofer Levy, a physician and director of a vaccine program at Boston Children’s Hospital. “It’s going to be hard to generate all the data we want in short order when a new variant emerges.”

According to many of the advisers, the best data on which to base decisions are what’s known as a “correlate of protection,” or a defined level of immune response that establishes whether someone is protected from disease or infection. So far, that information has been hard to obtain, although researchers are trying.

Without an established threshold for immunity, the FDA and other health agencies have had to rely on comparing antibody levels following vaccination, a process that Marks termed a “poor person’s immune correlate of protection.”

In debating COVID vaccine modifications, FDA officials and the agency’s advisers drew parallels to the system the U.S. and other countries use to update influenza vaccines each year. The process typically begins in February or March with the selection of the strains expected to be circulating the following winter, and allows for drugmakers to manufacture enough doses for fall vaccination drives.

Similarly, if U.S. health agencies hope to have updated COVID vaccines ready by the fall, clinical trials testing those shots will likely need to begin by next month for drugmakers to report results and have new doses made in time, a government official told the committee.

“If you’re not on your way to that clinical trial by the beginning of May, I think it’s going to be very difficult to have, collectively across manufacturers, enough product to meet that demand,” said Robert Johnson, deputy assistant secretary for the U.S. Biomedical Advanced Research and Development Authority, or BARDA.

Both Pfizer and Moderna are testing versions of their vaccines that are tailored to omicron, and Moderna is also studying a “bivalent” formulation that targets omicron and the original coronavirus strain. It’s not clear when results from the studies might be available.

It’s also uncertain whether omicron-specific boosters would offer greater or more durable immunity overall, particularly if the coronavirus mutates into a more evasive variant.

Trevor Bedford, a biostatistician at the Fred Hutchinson Cancer Research Center, told the advisers Wednesday that the emergence of another “omicron-like” variant is less likely than the virus evolving from omicron more gradually. But he also noted a wide range of probabilities for such a scenario, suggesting an omicron-like variant could arrive every 1.5 years to 10.5 years.

While the advisory committee did not vote on any specific proposals, they did resolve to meet again on the issue and some members suggested they play a more active role in guiding the process for updating vaccines.

“I feel like, at some level, the companies dictate the conversation here,” said Paul Offit, director of the vaccine education center at Children’s Hospital of Philadelphia. “It really has to come from us.”

For example, with influenza, the committee votes on which strains should be included in each year’s flu vaccine.

The role of the committee was already in focus after the FDA decided to move ahead with its authorization of a fourth dose in certain adults without consulting its advisers — a point raised early in Wednesday’s meeting.

Marks, in response to an adviser’s question, said the FDA felt that decision was not a major change and was “reasonable” in light of emerging data from the U.K. and Israel.

But he later acknowledged that giving a fourth dose of the same vaccines was a “stop-gap measure until we’ve got something in place for a potential next booster,” ideally one with longer-lasting protection. “We simply can’t be boosting people as frequently as we are.”