F.D.A. May Move Toward Updating Vaccines

WASHINGTON — A panel of independent experts advising the Food and Drug Administration will make its recommendation on Tuesday on whether to update existing Covid-19 vaccines to target a newer version of the coronavirus in a booster shot that Americans could get in the fall.

The federal government is hoping to improve the vaccine to better boost people’s immunity before a likely resurgence of the virus this winter. But in order for it to move that quickly, it may need to abandon the lengthy human trials that have been used to test coronavirus vaccines over the past two years in favor of a faster process that relies more on laboratory tests and animal trials.

The most recent trials with human volunteers have taken five months, even using relatively small groups. But the virus is evolving so quickly that new vaccine formulations are out of date before such trials are even finished.

Pfizer and Moderna, the two major vaccine manufacturers, have both been studying an updated vaccine that targets the Omicron variant that became dominant last winter. Both companies took a financial risk and started manufacturing that updated version, betting that the government would pick it to be the fall booster.

But Omicron itself was overtaken by a succession of subvariants starting nearly three months ago, and many scientists argue that it is a bygone threat.

“Omicron is clearly in the rearview mirror,” Dr. Peter J. Hotez, a vaccine expert with Baylor College of Medicine, said. A booster that targets Omicron makes no sense, he said, unless it also works against the latest subvariants, adding, “I haven’t seen evidence of that.”

At a meeting on Tuesday, the F.D.A. will ask the advisory panel whether a retooled vaccine should aim at a version of the virus in the Omicron family. That would leave it to federal regulators to decide exactly which formulation to use in the fall.

Scientists initially had high hopes for a so-called bivalent vaccine that would combine the existing formulation with one that targeted Omicron itself. Clinical trial results released this month by Moderna and Pfizer, with its partner BioNTech, found that it triggered higher levels of antibodies against Omicron than existing vaccines do.

But while the companies heralded the findings, outside scientists were not impressed by the less-than-twofold increase. Dr. Dan H. Barouch, a virologist at Beth Israel Deaconess Medical Center in Boston, described it as “relatively modest.” And the F.D.A., in a new briefing document for the advisory committee, said that the bivalent targeting Omicron is “already somewhat outdated.”

Federal regulators may instead push for a bivalent vaccine that would target BA.4 and BA.5, two subvariants of Omicron. They now account for more than one-third of the infections in the United States, and might be more akin to whatever incarnation of the virus is circulating in the fall.

But a bivalent that targets those subvariants would also be problematic. Neither Pfizer nor Moderna has concentrated on developing one, and no one knows for sure how well it would work. At this late point in the year, using human trials to such a vaccine, followed by the two months that would be required to manufacture doses, could push the release of any new vaccine well into the next wave of the virus.

That suggests that officials would have to base their judgments largely on animal trials and laboratory tests.

Dr. Kelly L. Moore, president of Immunize.org, a nonprofit group that works to increase immunization rates, said that such an accelerated process is already used to update the flu vaccine each year.

While this is the nation’s first stab at the next generation of Covid vaccines, she said, the existing ones have been safely given to hundreds of millions of people. Updating them might call for “very well-educated guesswork,” she said, but such deductions are “appropriate for the circumstances.”

If the government ends up going for a booster shot that targets BA.4 and BA.5, it will still be in a race to produce the doses by fall, even with accelerated testing. Pfizer may be able to meet an October deadline, according to two people familiar with the company’s operations.

But Dr. Paul Burton, Moderna’s medical director, said in an interview last week that it’s unlikely that the company could deliver doses until very late this year, or even early next year. “I don’t think we would be in a position to be prepared to support the fall booster campaign,” he said.

There is also the chance that the virus will evolve yet again and render the updated vaccine ineffective.

“Do we target BA.4 and 5? They will probably peak somewhere in the next month or two,” said Dr. John Beigel, a clinical research director at the National Institutes of Health who has conducted multiple coronavirus vaccine studies. “They may be old news by the time the fall comes.”

Dr. Beigel said one option is to simply stick with the existing vaccines, which continue to provide robust protection against severe disease, but very little against infection.

The Centers for Disease Control and Prevention has estimated that as of February, 60 percent of Americans had already been infected with the virus, providing them with at least some temporary immunity. While breakthrough infections among vaccinated individuals are now common, many of the cases are mild.

Still, the World Health Organization said this month that updated versions of the vaccines should be studied because of the rapid deterioration in protection against symptomatic illness.

Dr. Beigel and other public health officials say the virus is ever more agile at evading the antibodies that provide the first line of defense against infection. Studies show the existing booster shots trigger significantly lower level of neutralizing antibodies against BA.4 and BA.5 than they do against Omicron.

On average, 255 Americans still die of Covid daily, and about 4,400 are hospitalized. The F.D.A. briefing document said the risk of another major Covid outbreak will rise later this year “due to the combination of waning immunity, further evolution of variants, and increased indoor activity.”

The advisory panel will likely split between those who believe a fall booster will be broadly necessary and those who would limit additional shots to high-risk individuals. Dr. Arnold Monto, a public health professor at the University of Michigan who chairs the panel, predicted that a broad swath of the population will be offered booster shots.

“We know there’s waning,” he said in an interview. “We have to boost, and it’s better to boost with something more relevant” than the existing vaccines.

At the other end of the spectrum is Dr. Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia. “Hospitalizations are down. Deaths are way down because we are protected against serious illness,” he said. “That’s what matters.”

He said only people over 70 and those over 50 with serious underlying conditions will likely need a fall booster shot, because Covid infections in those groups could have serious consequences.

In the end, just how much the government has available to spend could determine the scale of a new booster campaign. Congress rebuffed a White House request for $22.5 billion in emergency coronavirus funds, and a compromise plan to spend $10 billion has been stalled since April. The government has shifted $5 billion in funds for coronavirus tests and protective equipment to buy new vaccines.

“With the resources that we’ve been able to pull together, cull together for vaccines for the fall, it’s very clear we’re not going to have enough vaccines for every adult who wants one,” Dr. Ashish Jha, the White House coordinator for the pandemic response said at a briefing last week.

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