A key U.S. Food and Drug Administration panel on Friday afternoon voted against a universal booster shot for the most popular COVID-19 vaccine. Instead, the panel endorsed a booster only for certain Americans: those 65 and older plus younger people who are at high risk of disease owing to underlying conditions.
The votes by the FDA’s Vaccines and Related Biological Products Advisory Committee, or VRBPAC, could narrow any effort by the health-safety agency to authorize a third shot for many of the 180 million (and counting) Americans who are fully vaccinated against COVID.
The FDA isn’t required to honor VRBPAC’s recommendations, although it almost always does.
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The panel’s first vote concerned a broad proposal to greenlight boosters for anyone 16 years of age or older who has already gotten New York-based Pfizer’s messenger-RNA vaccine. The two-dose Pfizer jab, one of three that the FDA has authorized for distribution, accounts for 55 percent of U.S. COVID inoculations.
The FDA has cleared a standard regimen of the Pfizer vaccine for Americans ages 12 and up, but VRBPAC only scrutinized boosters for those 16 and older. Pfizer a few weeks ago submitted data to the FDA that, according to the company, pointed to a broad need for boosters six months after initial vaccination.
But VRBPAC analyzed the data and, after an all-day virtual meeting, came away unconvinced that all Americans who’ve received the Pfizer vaccine need to reinforce their immunity. The vote was 16 to three, against.
When it came to boosters for older and more vulnerable Americans, however, the panel was unanimous. If you’re 65 or up or at high risk of disease, you should get boosted.
Now it’s up to the FDA to act, or not act, on that recommendation.
Wait, didn’t the FDA already authorize boosters?
Yes, but only for around 3 percent of Americans. The FDA on Aug. 12 gave emergency-use authorization to Pfizer and Massachusetts-based Moderna to offer third doses of their respective mRNA vaccines to the roughly 7 million Americans with immune disorders, eight months after their second doses.
Antibodies seem to fade more quickly in immunocompromised people than in people with healthy immune systems—hence the FDA’s urgency to approve boosters for that segment of the population.
But the FDA hedged on boosters for everyone else. “Other individuals who are fully vaccinated are adequately protected and do not need an additional dose of COVID-19 vaccine at this time,” Acting FDA Commissioner Janet Woodcock stated. “The FDA is actively engaged in a science-based, rigorous process with our federal partners to consider whether an additional dose may be needed in the future.”
Two weeks later, the FDA announced it was scheduling the Friday VRBPAC meeting to weigh the fresh batch of data from Pfizer. The data indicated the “vaccine effectiveness is waning over time,” the company claimed. “The totality of the available data supports the public health need for a booster (third) dose.”
Friday’s vote partially rejected Pfizer’s claim. Only the most vulnerable Americans need boosting, VRBPAC decided. The FDA could overrule the panel and back Pfizer, of course, but such a move would be all but unprecedented and could badly undermine public confidence in the agency.
If the FDA was in no hurry to consider boosters-for-all in August, what changed in September?
Delta, for one. While that more-dangerous new variant of the novel-coronavirus—“lineage” is the scientific term—was already widespread in August, it’s more widespread now, accounting for the overwhelming majority of cases in the U.SA.
And it’s driving a surge in infections. The United States registered 80,000 new COVID cases a day in early August, 130,000 a day in mid-August, and more than 150,000 a day through September.
The spike in infections coincided with a small number of breakthrough infections in fully vaccinated people. As of Sept. 7, the U.S. Centers for Disease Control and Prevention had counted more than 11,000 non-fatal breakthrough infections requiring hospitalization. By the same day, around 2,700 Americans had died of breakthrough COVID.
While that’s a vanishingly small proportion of the vaccinated population, it’s not nothing. And it might hint at a slow reduction in the effectiveness of the jabs.
One major study, led by Stephen Thomas at SUNY Upstate Medical University and published in The New England Journal of Medicine on Sept. 15, showed “a gradual decline in vaccine efficacy” in 44,000 fully-vaccinated trial subjects. Specifically, the mRNA vaccines’ ability to prevent symptomatic infection dwindled 13 points, from 96 percent to 83 percent.
The decline could have been worse, the researchers explained. An mRNA jab “prevents COVID-19 effectively for up to six months after the second dose across diverse populations, despite the emergence of SARS-CoV-2 variants,” they wrote.
Are we sure Delta is to blame for the decline in vaccine effectiveness?
No. It’s possible vaccine-induced antibodies were going to wane over time, regardless of which SARS-CoV-2 lineage was prevalent. “Vaccine effectiveness decreases with increasing time since being fully vaccinated, irrespective of variant,” Pfizer claimed in the data packet the company submitted to VRBPAC ahead of its Friday meeting.
In any event, the FDA panel wasn’t convinced that a slight decrease in effectiveness over time warranted a booster for younger Americans with healthy immune systems.
So what exactly is in the booster?
It’s the same formula that’s in Pfizer’s regular mRNA shot, and in the same quantity—30 micrograms.
Just how beneficial is a third shot?
Depends on who you are. Another study in The New England Journal of Medicine, led by Yinon M. Bar-On at the Weizmann Institute of Science in Israel and also published on Sept. 15, looked at a group of 1.1 million Israelis, age 60 or older, who got a booster shot of Pfizer at least five months after their second dose.
Twelve days after the third shot, severe COVID in this group declined nearly 20-fold.
This data clearly impressed VRBPAC. After all, people 65 and older account for around 80 percent of COVID deaths in the United States. Time and again, the data have underscored the greater risk the novel-coronavirus poses to seniors. As easy as it was for VRBPAC to reject boosters for Americans 16 to 64, it was even easier for the panel to endorse boosters for those 65 and up.
So the booster works for older people. But is it safe?
Yes. A study co-led by Angela Choi, Matthew Koch and Kai Wu that appeared in Nature Medicine on Sept. 13 assessed 19 people who got a third shot of Moderna’s mRNA vaccine six months after their second shot.
“The most common systemic [adverse reactions] after the booster doses were fatigue, headache, arthralgia and myalgia,” the researchers wrote. Basically, soreness and fatigue—same as with the first two doses. There were no serious side effects from the booster.
Why was Pfizer the only company asking for permission to offer boosters?
Of the three companies with FDA authorization to vaccinate Americans for COVID, only Pfizer submitted booster data for the VRBPAC’s Friday meeting. Neither Moderna nor New Jersey-based Johnson & Johnson asked for their jabs to be considered at this meeting.
In Moderna’s case, there are strong hints that that company’s vaccine creates more antibodies than Pfizer’s does, which implies that the protection the Moderna shot confers might be somewhat more durable.
A study of 1,700 people that appeared in The Journal of the American Medical Association on Aug. 30 detected 2,900 antibody units per milliliter, on average, in recipients of the Moderna jab. People who got Pfizer averaged less than half that—just 1,100 units per milliliter.
To be clear, both vaccines offer strong protection. It’s just possible that Moderna’s strong protection lasts a bit longer. Thus, there’s potentially less urgency for a booster for this vaccine.
As for Johnson & Johnson, that company only recently—Aug. 25— completed its own internal trial of a booster for its single-dose vaccine. “We have established that a single shot of our COVID-19 vaccine generates strong and robust immune responses that are durable and persistent through eight months,” Mathai Mammen, the firm’s head of research, said in a statement.
Johnson & Johnson has shared the data with the FDA, but the feds haven’t acted on it yet.
Is there a downside to boosting Americans?
From a certain point of view, yes. A paper co-written by infectious disease experts Marion Gruber, Philip Krause and others, and which appeared in The Lancet on Sept. 13, weighed the benefit of boosters in the United States versus the need for first shots in underserved countries.
“Current evidence does not … appear to show a need for boosting in the general population, in which efficacy against severe disease remains high,” the authors asserted. Notably, Gruber and Krause both work for the FDA, but plan to leave the agency in coming weeks.
The doses that younger, healthier Americans would consume getting boosted could have much greater impact if authorities sent them abroad to countries that are struggling to keep up with demand for vaccine, Gruber, Krause and their co-authors wrote. “The limited supply of these vaccines will save the most lives if made available to people who are at appreciable risk of serious disease and have not yet received any vaccine.”
“Even if some gain can ultimately be obtained from boosting,” they added, “it will not outweigh the benefits of providing initial protection to the unvaccinated.”
