In the United States, it’s looking like booster shots of Pfizer-BioNTech’s COVID-19 vaccine won’t be available to the general public at large starting this week.
A panel of expert advisers to the U.S. Food and Drug Administration unanimously recommended September 17 that boosters next be allowed for only certain groups: people 65 years and older, individuals at high risk of severe COVID-19 and those with jobs that put them at high risk of exposure.
That’s more limited in scope than what the Biden administration proposed in August. Officials had announced plans to offer a third dose of Pfizer-BioNTech’s vaccine to the general public at least six months after vaccination starting September 20, pending an OK from the FDA.
Since officials unveiled that plan, it’s been widely debated. Some researchers — including Pfizer scientists — argue that because the vaccine’s protection against infections is waning, that could foreshadow a possible dip in protection against severe disease too. So the time to bolster everyone’s protection with a third dose is now, these researchers say. But others disagree, contending that it’s more important to focus on getting doses to unvaccinated people first, and that many younger, healthy vaccinated people remain well-protected against severe disease and death after just two doses.
Third doses are already authorized for moderately to severely immunocompromised people who may not develop good protection from the initial shots (SN: 7/23/21). The case for another dose was obvious for that group, says Mark Slifka, a viral immunologist at Oregon Health & Science University in Portland who wasn’t involved with the FDA panel. The data were “clear as day that the third dose was important” and could help boost the levels of protective antibodies in some patients.
But moving forward for the general population requires more specialized consideration, Slifka notes. “I think part of it comes down to what’s our level of risk tolerance.”
It’s still unclear when and for which new groups the FDA will authorize booster shots. A separate panel of expert advisers to the U.S. Centers for Disease Control and Prevention is expected to weigh in on booster shots September 22 and 23. Whatever the new guidance is, it will apply only to people who received Pfizer-BioNTech’s COVID-19 vaccine. Decisions for Moderna’s or Johnson & Johnson’s jabs still lie ahead.
Here are some of the key questions that influenced the FDA panel’s recommendation.
Is vaccine effectiveness starting to wane?
COVID-19 vaccines are still largely keeping people out of the hospital in the United States, studies show (SN: 8/31/21). Even as infections among vaccinated people go up, protection against hospitalization and death remains high, CDC epidemiologist Sara Oliver said at the September 17 meeting.
That’s true for all three vaccines — developed by Pfizer-BioNTech, Moderna and Johnson & Johnson — available in the United States even with the spread of the highly contagious delta variant. Before delta dominated in the country, estimates of vaccine effectiveness against hospitalization in adults 18 and older ranged from 84 to 97 percent. That’s compared with 75 to 95 percent effectiveness after the variant took over, Oliver said. Effectiveness against infection, on the other hand, has dipped from 72 to 97 percent before delta to around 40 to 84 percent.
Still, data from Israel — the first country to vaccinate the majority of its population against COVID-19 — hint that over time Pfizer-BioNTech’s COVID-19 vaccine becomes less effective at preventing severe disease, particularly in people age 60 and older. That trend spurred public health officials there to begin offering a booster dose to that age group July 30 amid a spike in cases.
That third dose seems to have helped. People age 60 and older who didn’t receive a booster were 11 times as likely to be infected with the coronavirus and nearly 20 times as likely to develop severe disease compared with those who got a third dose at least 12 days earlier, researchers reported September 15 in the New England Journal of Medicine. Preliminary data presented at the September 17 meeting suggest that the same trend may occur in people ages 40 to 59.
The booster brings vaccine efficacy back up to levels seen before delta came on the scene, Sharon Alroy-Preis, head of public health services at Israel’s Ministry of Health, told the FDA panel. “It’s like a fresh vaccine.”
It’s less clear, however, that protection against the worst of COVID-19 wanes in younger people, too, contributing to the FDA panel’s recommendation for boosters for those age 65 and older. But that should become clearer in the coming months, as researchers continue to monitor the situation.
In Israel, everyone over age 12 became eligible on August 29 for a third shot at least five months after a second dose. That decision was made because officials wanted to control the latest surge in cases, and limiting transmission would have been difficult without vaccinating everyone eligible, Alroy-Preis said.
Estimates suggest that transmission in Israel is indeed slowing. By one measure, infected people tend to pass the virus on to fewer than one other person, meaning the outbreak could begin to fizzle out. While hospitalizations and severe cases have stabilized since people began receiving boosters, however, the overall number of COVID-19 cases remains high.
That disparity may exist because the country opened schools on September 1 and many Israelis have gathered in holiday celebrations, Alroy-Preis said. But once things settle down, officials will likely have a better sense of where things stand. “We feel the booster effect, but we are not over the fourth wave yet,” she said.
How safe is it to give people a third dose?
Many experts on the FDA panel expressed concerns about the possibility of heart inflammation, a condition called myocarditis, that has been linked to mRNA vaccines such as Pfizer-BioNTech’s, particularly in young males (SN: 6/1/21). Most cases are mild and are easily treated.
Experts have determined that the benefits of COVID-19 vaccines to prevent severe disease outweigh the risk of myocarditis. But most panelists were reluctant to come to the same conclusion for a booster dose for younger age groups without more data.
Since boosters started rolling out in Israel, officials so far have documented only one case of myocarditis out of 2 million doses — in a male in his thirties. However, not enough time has passed to know for sure: Most younger people received a third dose within the last two weeks. Officials are actively monitoring for myocarditis reports, Alroy-Preis said. In Pfizer-BioNTech’s clinical trial testing a third dose, none of the more than 300 participants developed myocarditis.
But that data did little to alleviate the concerns of the FDA panel. Not only is the picture from Israel not yet certain, but some panelists were also concerned that the Pfizer trial included too few people.
More than a million third doses have been given in the United States, noted Hayley Gans, an infectious disease pediatrician at Stanford University, at the meeting. So there could be a larger pool of safety data to consider. But without that data available, it feels like trying to make a decision without all the pieces, Gans said. Oliver, the CDC epidemiologist, said that the data would probably be released in the coming days.
Aside from the uncertainty surrounding myocarditis, a third dose appears safe. Side effects like pain at the injection site, fever and chills were mostly mild and occurred at similar rates as after a second dose.
How long might the boost in immunity last?
No one knows for sure, but increasing the time between doses does traditionally prompt longer-lasting vaccine protection, Slifka says. While that’s not always the case, “I doubt [any COVID-19 booster] will be shorter-lived than what we have,” in terms of immunity, he says. “It’s either going to be equal to or longer” than at least six months.
Giving people a third dose of Pfizer-BioNTech’s vaccine does boost antibodies to levels that surpass those seen after a second dose, researchers reported September 15 in a separate study in the New England Journal of Medicine.
But, crucially, researchers don’t yet know what level of antibodies in the blood actually gives a person sufficient protection against the coronavirus in the first place. That would be helpful to pinpoint whether immunity, either after two or three doses, might have waned, James Hildreth, president of Meharry Medical College in Nashville, said during the FDA panel’s discussion.
Immunologist Michael Kurilla agreed. “We just can’t simply be in a position where we would just be vaccinating people every time we think there’s a problem,” so researchers need to get a better handle on how to measure protection, said Kurilla, of the National Institutes of Health’s National Center for Advancing Translational Sciences in Bethesda, Md.
What’s more, our immune systems have the tools to remember the coronavirus after vaccination, which should prevent severe disease, Kurilla noted. And just two doses of Pfizer-BioNTech’s vaccine seem to spark long-lived immune memory — including cells that make antibodies as well as other immune cells that coordinate the immune response or kill infected cells — so the body can rapidly ramp up defenses if the coronavirus were to invade.
Booster shots could be useful to fortify weak immune memory, giving people better protection in the future. But given that many people already have developed that strong, long-lived immune memory, it’s unclear why they would even need a third jab right now, Kurilla said.
Our immune systems don’t work as well as we age, however. So older people may end up needing those boosters more than younger people.
How would boosters affect the pandemic more broadly?
Researchers on the FDA panel were divided on the answer to that question.
The effects of a third dose on controlling COVID-19 cases and spread in the United States would probably be minimal, some said. That’s partly because in this country, virus transmission is largely driven by high numbers of unvaccinated people, said Eric Rubin, a microbiologist and infectious disease physician at the Harvard T.H. Chan School of Public Health. So, giving boosters to vaccinated people could have little impact on spread overall.
Others, including Gans, said that to answer the question, they would like to see more data on the booster’s ability to curb transmission. If that data did show that fewer people are getting infected by people who have had three shots, then giving some people, such as parents or teachers, a vaccine booster to better prevent infection and spread might help protect kids who are too young to be vaccinated.
What’s more, many experts around the world emphasize that to have the most impact on the pandemic, efforts should be focused on getting vaccines to the unvaccinated, not boosters to the vaccinated(SN: 2/26/21). In a push for vaccine equity, the World Health Organization has called for a moratorium on boosters until the end of the year. The vast majority of vaccine doses have made it into arms in high-income countries, while most people in low-income countries still lack protection, WHO Director General Tedros Adhanom Ghebreyesus said at a September 8 news briefing. “We have been calling for vaccine equity from the beginning, not after the richest countries have been taken care of.”
What about boosters for Moderna’s and Johnson & Johnson’s vaccines?
Most of the focus on boosters has centered on Pfizer-BioNTech’s COVID-19 vaccine, in part because Pfizer was the first pharmaceutical company to ask for booster approval from the U.S. Food and Drug Administration. But millions of U.S. residents have received vaccines developed by Moderna or Johnson & Johnson. What do we know about potential boosters for those vaccines?
For now, Moderna’s vaccine appears to be outperforming Pfizer-BioNTech’s, meaning that boosters might be less crucial. (Although a third dose does raise antibody levels, even against coronavirus variants, the company says.) When it comes to hospitalizations, Moderna’s shot was 93 percent effective at keeping people out of the hospital as of August 15, researchers reported September 17 in Morbidity and Mortality Weekly Report. That’s compared with an estimated 88 percent effectiveness for Pfizer-BioNTech’s vaccine.
It’s unclear why there might be differences in effectiveness between the two vaccines, since both rely on the same mRNA technology. But it’s possible that the longer interval between first and second doses — four weeks for Moderna’s compared with three weeks for Pfizer’s — may help people develop a longer-lasting immune response, says Mark Slifka, a viral immunologist at Oregon Health & Science University in Portland. Plus, Moderna’s vaccine includes a higher dose than Pfizer’s does, which could also help.
Fewer people have received Johnson & Johnson’s single-dose COVID-19 vaccine than the mRNA vaccines, so there’s less information available on that shot. As of August 15, a single dose was around 71 percent effective at preventing hospitalization, researchers reported in that same September 17 study. That’s close to the nearly 75 percent efficacy against severe disease reported in late-stage clinical trials. And there’s no evidence that protection wanes over time, the company said in a September 21 news release.
But a second dose given two months after the first can increase antibody levels and provide even better protection, Johnson & Johnson also announced. In clinical trials, that second shot had an efficacy of 94 percent against symptomatic COVID-19 in the United States, on par with the mRNA vaccines.
Waiting six months to give the second dose helped boost antibody levels even more, the company said. While the two-month-interval raised antibodies four to six times as high as after the first dose, six months between doses resulted in levels 12 times as high as a month after that second shot. And more antibodies could mean more protection against COVID-19.
Booster data for these other shots are on the docket for the FDA to consider in the future. That could perhaps happen in a few weeks’ time, National Institute of Allergy and Infectious Diseases director Anthony Fauci told NBC News’ “Meet the Press” on September 19.
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