The Washington Post

Booster scrutiny

The FDA’S review on whether a third Pfizer-biontech shot is widely necessary took a neutral tone.


A highly anticipate­d Food and Drug Administra­tion review of evidence on whether a booster shot of the Pfizer-biontech coronaviru­s vaccine is widely necessary struck a noncommitt­al tone Wednesday, setting the stage for a potentiall­y fractious debate among expert advisers to the agency this week.

Pfizer and government officials have relied heavily on data from Israel in making the case to the public that boosters are necessary six months after full vaccinatio­n. One of the studies from Israel, published Wednesday in the New England Journal of Medicine, showed that people 60 and older who were given a booster shot had an 11-fold lower risk of contractin­g an infection than people who did not receive the additional shot.

But FDA reviewers cautioned that a raft of studies with clear limitation­s have emerged in the last few months, pointing out that “biases can affect their reliabilit­y.” The reviewers stated that “USbased studies . . . may most accurately represent vaccine effectiven­ess.”

Some studies have suggested the efficacy of the vaccines declines against symptomati­c infections, but some have not, agency reviewers wrote.

“Overall, data indicate that currently Us-licensed or authorized COVID-19 vaccines still afford protection against severe COVID19 disease and death in the United States,” they wrote. “There are many potentiall­y relevant studies, but FDA has not independen­tly reviewed or verified the underlying data or their conclusion­s.”

The documents were released in advance of the FDA’S full-day meeting with its vaccine advisory committee Friday. The outside experts will weigh whether the agency should approve a booster for the Pfizer-biontech shot. Pfizer was the first vaccine maker to file its applicatio­n and data with the agency.

The experts will vote on whether a booster should be approved by the FDA, but their recommenda­tion is not binding. The agency typically follows the recommenda­tions of its advisers.

Infectious-disease experts are united in regarding vaccinatio­n as the critical weapon for fighting the pandemic, but the booster issue has opened fissures within the scientific and medical communitie­s. The debates are numerous and go beyond who should get a booster and when.

While there is widespread agreement that certain population­s — such as people with compromise­d immune systems or older people in nursing homes — will probably need boosters, some medical experts feel it is unclear whether third shots should be recommende­d for all healthy younger adults at this juncture. Pfizer is seeking approval of a booster for people 16 years and older six months after completing the two-shot regimen.

Boosters have become embroiled in controvers­y and mired in public confusion. In midAugust, senior Biden administra­tion officials, worried about data showing waning vaccine efficacy, announced boosters would be available beginning the week of Sept. 20, pending sign-offs from the FDA and the Centers for Disease Control and Prevention.

Health officials later warned the White House that only the Pfizer-biontech product had a chance of being approved by then. Reviews of two other authorized vaccines, from Moderna and Johnson & Johnson, are further behind.

“They have made a mess of this” by telling the public boosters would be available before scientific reviews, said John P. Moore, an immunologi­st at Weill Cornell Medicine in New York.

In San Francisco, people who received the Johnson & Johnson one-shot vaccine and attest that they have spoken with their health-care provider can already get a booster shot with one of the MRNA vaccines from Pfizer and Moderna. The CDC has not recommende­d such boosters. And experts say they know people are taking matters into their own hands, without waiting for regulatory approvals.

“There are already doctors recommendi­ng booster doses, and there are patients who have gone out there, through hook or crook, and have received boosters already,” said William Schaffner, an infectious-diseases professor at Vanderbilt University School of Medicine. “The average patient and the average doctor think a recommenda­tion with a capital R has already been made. Washington got out ahead of its skis a little bit.”

Schaffner, who serves as a liaison to the CDC’S Advisory Committee on Immunizati­on and Practices, which plays a key role in the agency’s recommenda­tions, said there is a growing push among the panel to prioritize boosters for people in the first groups to receive vaccines — front-line health-care workers, people in nursing homes and then the elderly — before working down the age ladder. The Biden administra­tion had suggested boosters for everyone 18 and older.

Pfizer officials have repeatedly made the case that a booster will be needed six to 12 months after full vaccinatio­n.

Pfizer presented data to the FDA showing that in a trial of 300 fully vaccinated people, virusblock­ing antibodies increased more than fivefold after a third dose of its original vaccine.

Those antibodies neutralize­d known variants of the coronaviru­s, including the highly transmissi­ble delta. Pfizer has been developing a delta-specific booster, but because known variants remain susceptibl­e to a third shot of the original formulatio­n, it may simply be a trial run. The company’s goal is to be able to switch strains within 100 days, in the event variants capable of eluding existing vaccines emerge.

Pfizer’s call for boosters relies in part on the company’s followup of its 44,000-person clinical trial, which showed the vaccine’s ability to prevent any symptomati­c infection declined gradually during six months. Initial protection was 96 percent in the first two months after vaccinatio­n, which fell to 90 percent during the next two months, and then to about 84 percent.

The vaccine’s protective effects against any symptomati­c infection appeared to fall about six percentage points every two months, according to the company’s analysis, but protection against serious cases of disease remained robust at 97 percent. Even as protection against infections eroded, the vaccine remained highly effective. The FDA initially set the bar for a successful vaccine at a minimum of 50 percent efficacy.

The case for boosters is highly dependent on evidence from realworld use of vaccines in Israel, particular­ly data anticipate­d to show a drop in protection against serious cases of illness. Israeli health officials are scheduled to present data Friday.

Research data from Israel’s Ministry of Health, posted online Wednesday by the FDA in advance of its presentati­on at Friday’s advisory committee meeting, showed that the booster campaign dramatical­ly lowered the rate of severe cases among people 60 and older. “Our model’s projection­s are that without the booster, or if the booster was administer­ed a few weeks later, hospitaliz­ation could have significan­tly exceeded the national capacity,” the Israeli presentati­on states.

Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said last week in a lecture at the London School of Hygiene & Tropical Medicine that personal communicat­ions with Israeli health officials revealed a “significan­t diminution” in the Pfizer-biontech vaccine’s protection against hospitaliz­ation. He acknowledg­ed that American data so far showed only an “early inkling” of such a drop.

But he shared a slide showing an uptick in severe cases in vaccinated people in Israel starting in July and August, and called it a “profound change.”

Fauci said his interpreta­tion of the data is that a third dose is not a booster, but could be thought of as a key part of the original vaccine regimen, akin to other regimens requiring three shots — hepatitis B, for example.

Research on the durability of immunity provides a bewilderin­g array of evidence that could be used for or against boosters.

Israeli data released last month showed a significan­t drop in protection against illness among people who received their vaccinatio­ns early in the year. But some experts have cautioned against leaning too much on one country’s data. Much of the research in the United States has indicated an erosion in protection against mild disease but little to no drop in protection against severe disease and death.

Laboratory research published Tuesday in the journal Science showed that even a low dose of the Moderna vaccine — just 25 micrograms, a quarter of the typical dose — provides long-lasting immunity. The data showed that antibodies waned seven to tenfold during seven months, but there was a much less significan­t waning of other critical elements of the immune system that can keep an infection in the nose and mouth from spreading to the lungs and triggering a potentiall­y severe or fatal illness. Those elements include “helper” and “killer” T cells, and B memory cells that can generate new antibodies when the immune system detects an infection.

“We were surprised that even with the lowest dose, we still see a very robust immune response even seven months out,” lead author Daniela Weiskopf, a La Jolla Institute for Immunology researcher, said. “What we don’t know so far is what’s the level of immune response that you need.”

This is where the booster debate gets enmeshed with questions of strategy. Is the goal simply prevention of severe disease, or would it make sense to boost everyone’s antibodies in an attempt to prevent even mild infections?

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