FDA expected to authorize second coronavirus booster for 50 and older
The Food and Drug Administration is poised to authorize a second coronavirus vaccine booster for anyone 50 and older, a bid to provide an extra layer of protection amid concerns Europe’s rise in infections from an omicron subvariant could hit the United States, according to several government officials.
The authorizations for second Pfizer-BioNTech and Moderna boosters could be announced as soon as Tuesday, according to the officials, who spoke on the condition of anonymity because they were not permitted to discuss the situation. They said talks continue, and it was possible, but unlikely, that major changes could occur.
After the FDA acts, Rochelle Walensky, director of the Centers for Disease Control and Prevention, is expected to issue a statement saying second boosters are available for eligible individuals interested in receiving them but not to explicitly recommend that.
People will be able to get a second booster at least four months after receiving the first booster. Currently, second boosters are recommended only for people whose immune systems are impaired, which can hamper an effective response to the vaccine.
The question of additional boosters has sparked days of discussion among health officials in the Biden administration and debate within the wider scientific community. Administration officials, as with past vaccine decisions, have struggled to decipher intriguing but frequently evolving data, often from Israel; a political environment in which large swaths of the American population are ambivalent — or in come cases, hostile — toward vaccines; and uncertainty about whether the highly transmissible omicron subvariant BA.2 poses a major threat.
The authorizations appear unlikely to prompt large numbers of older Americans to rush to get a second booster. Data suggests that vaccine fatigue has set in for many, even among some of the most vulnerable. About two-thirds of those 65 and older that are eligible for boosters have received them, according to the CDC. Overall, U.S. vaccination and booster rates are lower than in many Western European nations — which nevertheless have experienced a sharp rise in cases in recent weeks and months.
In deciding to make fourth shots of the mRNA vaccines available for people 50 and older, the FDA considered and then rejected several alternatives. Officials described the discussions among administration health experts as lively but not antagonistic, with an effort to come to a unified position that could be clearly explained to the American people.
“There really was not a lot of debate there,” said one of the officials, adding that Walensky and the new FDA commissioner, Robert M. Califf, both supported the 50 and older approach.
There were initial differences among the agencies, however.
FDA officials favored second boosters for older people in part because of concerns about the spread of BA.2. The omicron subvariant accounts for about 35 percent of new cases in the United States, according to the CDC. In some parts of the country, BA.2 is the cause of more than 70 percent of new cases, according to a genomics testing company.
In contrast, CDC officials raised questions about whether second boosters were an immediate necessity. A recent CDC study showed that the vaccinations and boosters most commonly used in the United States provided robust protection for older and younger people against death or needing mechanical ventilation, even as protection against mild illness waned over time.
The discussions started by focusing on a threshold of 65, because that was the age in the authorization request for the Pfizer-BioNTech vaccine. Moderna asked the agency to allow adults 18 and older to receive a second booster.
Health officials also considered greenlighting boosters for people 60 and older to coincide with the data from Israel, which recently made fourth shots available for that age group, and has supplied a good deal of the available data on second boosters.
Some officials at the CDC and elsewhere in the administration expressed concern that setting the bar at 60 or 65 would prevent access to second boosters by younger members of medically underserved groups, including Latinos and Blacks. These groups have higher rates of underlying medical conditions at younger ages and have been disproportionately hurt by the pandemic. The life expectancy of Black Americans is shorter than that for White Americans.
In a pivotal meeting Wednesday night, attended by representatives of the major health agencies, officials agreed to set the age at 50. The decision to lower the age to 50 addressed a health equity concern, and also a desire to avoid the confusion that followed earlier administration efforts to describe which individuals with underlying medical conditions were eligible for an initial booster shot.
On Thursday came news that reinforced the move to provide second boosters to older people.
An Israeli study, not yet peer-reviewed, in more than half a million adults 60 to 100 years old found that a second booster provided significant protection against death from covid-19. Of 328,597 people who received a second booster during a 40-day study period early this year, 92 recipients died; among the 234,868 who had only one booster, 232 people died.
“Our study demonstrates that among the older adult population that had received a first booster dose at least four months earlier, mortality due to covid-19 during the omicron surge was significantly lower among those who had received an additional booster dose,” said researchers from Ben-Gurion University.
Unlike with some past vaccine decisions, the CDC will not directly recommend the second booster in part because the data is not robust, especially in the younger-than-60 group. The agency wants to give permission for a second booster to people who desire that. If officials conclude later that an annual coronavirus booster will be needed in the fall for the broader population, the agency could issue a recommendation.
Experts have differing views on boosters.
“If we go with what we have seen with previous waves of the pandemic so far, it is likely that these waning of antibodies will impact on protection against severe disease outcomes in older age groups,” said Boghuma Titanji, an infectious-diseases expert at Emory University.
“Starting a second booster program ahead of the winter and fall season may allow us to get ahead of a surge and be better prepared than we were with omicron,” Titanji said in an email. But she noted that among younger healthy individuals, the added benefit of a second booster is unclear.
Peter Hotez, a professor of pediatrics and molecular virology at Baylor College of Medicine and co-director of the Texas Children’s Hospital Center for Vaccine Development, said he strongly supports a second booster for people 60 and older, based on the Israeli data.
“The Israeli data is not perfect, but that is all we have,” Hotez said.
Although the shots are intended mainly to prevent serious illness and death, Hotez said he doesn’t want to get even a mild case of the coronavirus because of potentially severe aftereffects that are not well understood.
“I don’t want to get long covid, gray matter brain degeneration and cognitive decline,” Hotez said.
But Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, said he wanted to see more data on boosters for older groups.
“One of the things I am trying to think through is at what point do we say we can’t boost our way out of the pandemic,” he said. “We need better vaccines. I am begging for a vaccine 2.0 or 3.0.”
The issue of second boosters for older people is not scheduled to be presented to outside advisory committees of the FDA and the CDC, because officials view the change as incremental. In the past, the FDA vaccine advisory committee has pushed back on some of the agency’s efforts to expand access to vaccines.
Vaccinations have all but ground to a halt in the United States, with initial doses and boosters plummeting to the lowest levels since the program began in December 2020. Last Wednesday, the seven-day average of vaccinations fell to fewer than 182,000 a day, according to data compiled by The Washington Post.
A broader question is whether and when all eligible adults will need a fourth dose of the mRNA vaccines. That will be discussed April 6 by the FDA’s outside vaccine experts, who will also consider which factors might prompt a change in the composition of vaccines to deal with potential variants.
Anthony S. Fauci, chief medical adviser to President Biden, recently talked about fourth doses on Washington Post Live. A second booster, he said, increases individuals’ virus-fighting antibody level “to where it was originally with the third dose, but not above and beyond it.”
But he suggested that successive boosters might spur the responses of other parts of the immune system, including memory B-cells, that are capable of fighting off pathogens for stretches of time.
“That’s not easily measurable, and it may be that multiple boosters do incrementally increase that,” he said.
Who Should Get a 4th Covid Shot?
As coronavirus case counts continue to plummet across the United States, people’s immunity may be declining, too. Several studies have found that while mRNA booster shots have been successful at preventing hospitalization and death, their effectiveness against infections is waning.
It’s no wonder, then, that late Thursday, Moderna sought emergency use authorization from the Food and Drug Administration for a second booster shot for all adults. The company’s request came just days after Pfizer and BioNTech filed for emergency authorization for a second booster of its coronavirus vaccine for people 65 and older.
Moderna said that its much broader request would give the Centers for Disease Control and Prevention, as well as health care providers, more flexibility in determining who would benefit most from getting an additional booster shot and when.
Scientists and physicians are sharply divided over this. “I don’t think everybody should get another booster right now,” said Dr. Yvonne Maldonado, a pediatric infectious diseases physician at Stanford University. “But I don’t see any reason why we shouldn’t start to review the data that is available.”
Who is currently eligible for a fourth vaccine dose?
As of now, the only people authorized for a fourth dose are those with weakened immune systems. This includes teenagers and adults who have had organ or stem cell transplants, are undergoing chemotherapy for cancer, have advanced or untreated H.I.V. or are on immune-suppressing drugs.
It’s hard to predict how soon — or if — the F.D.A. might authorize a second booster (or fourth dose) for all adults. The agency is expected to convene an advisory committee next month to discuss the issue. And while experts say it’s reasonable that the committee might move swiftly on Pfizer’s application for older adults, it is unclear if Moderna’s more sweeping request will get the green light.
“We know that people over the age of 65, even when vaccinated, have a higher risk of dying than people under the age of 65,” said Dr. Carlos del Rio, an infectious disease specialist at Emory University. “That gets lowered significantly if people get boosted.”
One reason older adults may benefit from an additional booster shot is because as the immune system ages, it tends to weaken and does not produce the same quantity or quality of antibodies as it did when it was younger. On top of that, older adults often have other medical conditions that take up the body’s attention, putting them at higher risk of severe disease, said Dr. Christian Gaebler, an immunology researcher at Rockefeller University in New York City. “Diabetes, hypertension, obesity and chronic kidney disease are all risk factors for severe Covid,” he said. “And we know that these usually manifest in older age.”
In their justification for seeking second boosters for people 65 and up, Pfizer and BioNTech relied heavily on evidence from two studies conducted in Israel that suggested that people who had received fourth shots were less likely to become infected with the virus compared with those who had received three doses.
In one study, published on a preprint server in February, scientists reviewed the health records of about 1.1 million people over 60 who had received a fourth dose and compared them with those who had received just three doses. They found that the rate of confirmed infections, as well as that of severe illness, was lower in people who had gotten their fourth shot.
The second study, published Wednesday in The New England Journal of Medicine, looked at Israeli health care workers of all ages and found that both Pfizer’s and Moderna’s fourth shots bolstered antibody levels, though they were not very good at preventing infection.
Experts, however, cautioned that the available data is still preliminary and has not yet shown how long the benefits of a fourth dose will last.
If the shots are authorized for seniors, how should they think about timing them?
Experts tracking Covid-19 are careful not to give specific advice on when to get a fourth dose when the safety and efficacy data are still limited.
If another surge is just around the corner, for instance, seniors may benefit from getting an extra shot as soon as it’s authorized. But if the next wave doesn’t occur until the summer or even the fall, getting a booster now could backfire because the recipients’ immunity might start to wane by the time they need protection the most. Current vaccines are based on the original strain of the coronavirus, so getting a booster now may also do little to protect against future variants.
“It would be great if we knew exactly when the next wave was going to be so we could vaccinate people beforehand,” said Dr. Amy Sherman, an infectious disease physician at Brigham and Women’s Hospital in Boston. “But I think we’re not quite at the point where we know a clear seasonality, and we know the exact tempo and dynamics of Covid and newer variants.”
That being said, if a fourth shot is authorized for adults over 65, and it has already been several months since they got their first booster, “I would start thinking about whether I need a booster now,” Dr. del Rio said.
What does this mean for everyone else?
For people younger than 65, who are otherwise healthy, most experts agree that three doses are most likely enough for now. Those in their 20s and 30s who have already received three shots of the vaccine, for instance, will only see marginal benefits in protection from an additional shot, Dr. Gaebler said.
“Fourth doses might turn out to be advisable,” he said, “but at this point I think the focus should be on administering third doses.”
Dr. del Rio agreed. “I’m more concerned about the millions of Americans who are not vaccinated or are only partially vaccinated,” he said. “That, to me, is where we need to put our major focus.” Getting more people vaccinated, nationally and globally, could potentially have a bigger effect on reducing virus transmission and curtailing new variants so that everyone can return to normal life, Dr. del Rio said.
And there is hope that better vaccines and treatments are on the way. Pfizer and Moderna are testing new Omicron-specific versions of the Covid booster. And other researchers are investigating vaccines that boost mucosal immunity in the nose, as well as protein-based shots that may be better at protecting against the coronavirus in the future.
“We have to really think carefully about our vaccine strategies,” Dr. Sherman said. “We have to think as a society about what our goal is with repeated boosters and vaccines because none of our existing vaccines completely prevent transmission or prevent all disease. And so at what point are we comfortable with asymptomatic or mild infection in the population while still being able to protect those who are vulnerable?”
This article first appeared on The New York Times and was republished with