Many parents in the U.S. have been waiting to hear that the nation’s youngest children—those under 5 years old—can be vaccinated against COVID-19. Finally, on June 15, an expert panel convened by the U.S. Food and Drug Administration (FDA) said that two vaccines, made by Pfizer-BioNTech and Moderna, are safe and effective for children ages 6 months and older.
The FDA’s panel voted unanimously—21-0—that the benefits of Moderna’s vaccine outweigh its risks for kids ages 6 months through 5 years of age. They also voted unanimously that the benefits of Pfizer-BioNTech’s vaccine outweigh risks for kids ages 6 months through 4 years.
The FDA usually follows the recommendations of its advisory committee and is thus expected to authorize the shots for emergency use. Assuming it does, the vaccine advisory group of the U.S. Centers for Disease Control and Prevention (CDC) will review the data and decide whether to make a formal recommendation for vaccination in this age group.
If the CDC recommends the vaccine, children ages 6 months to 5 years old could get their shots as soon as next week, becoming the last age group eligible for vaccination against COVID-19. While rates of COVID-19 in this population are relatively low, rates of hospitalization are slowly increasing, possibly due to the dominance of the Omicron variant. According to the latest data from the CDC, more than 2 million cases of COVID-19 have occurred among children 4 years old or younger since the start of the pandemic, leading to more than 440 deaths.
While members of the FDA committee widely felt that parents should be able to vaccinate their young children against COVID-19, some argued it’s important to keep the disease’s relatively modest effects on kids in perspective. In response, Dr. Arthur Reingold, head of epidemiology at the University of California, Berkeley’s School of Public Health, noted that kids are routinely vaccinated against diseases that carry low risks of hospitalization and death—and COVID-19 should be no different.
Other committee members said vaccination’s benefits don’t stop at preventing disease. The shots could also reduce kids’ odds of developing complications like Long COVID and offer some freedom to families that have remained largely isolated until their youngest members could be vaccinated.
The Pfizer-BioNTech vaccine for kids ages 6 months to 4 years old is a three-shot regimen, and each dose is one-tenth the dosage given to adults. Children would receive two doses three weeks apart, and a third dose at least two months later.
In a company study involving more than 4,500 children, antibody levels generated by these children were compared to those produced by vaccinated people ages 16 to 25 years old. This allowed researchers to infer how much those antibodies protected against COVID-19. In the pediatric group, three-dose vaccine efficacy against symptomatic disease was 80.4% during a time when Omicron was circulating widely in the U.S.—though that estimate was based on such a small number of cases that it’s difficult to draw firm conclusions about how protective it is in real-world situations.
It’s been a long road for the Pfizer-BioNTech vaccine. The companies began submitting their vaccine for FDA authorization in this age group last December, after gathering data on a two-dose course. But those two doses generated relatively low levels of immunity, in part because they were tested while Omicron was dominating the U.S. That prompted the FDA and Pfizer-BioNTech to hold off on reviewing that data until the companies provided additional information on whether adding a third dose would increase levels of virus-fighting antibodies, and therefore immunity, against COVID-19. The company reported those data in May.
Moderna’s vaccine for children ages 6 months through 5 years old is given in two shots, and each dose is one-quarter the dose of that used in adults. Those immunized with Moderna would get two doses spaced four weeks apart.
Moderna tested its two-dose vaccine in more than 6,300 children. Among those ages 2 to 5, the shots were about 37% effective at preventing symptomatic disease when Omicron was prevalent. For kids ages 6 months to 2 years, efficacy was around 50% against symptomatic disease.
Pfizer-BioNTech shifted to a three-dose schedule after trial results showed that two of their kid-sized doses did not prompt a strong enough immune response. During the FDA meeting, Pfizer officials said their goal was to avoid side effects like fevers, which could dissuade parents from getting their kids vaccinated.
While the dosages also differ between companies, both will give the youngest children lower doses than those used for adults and older kids, in order to best balance the protective benefits against the potential risks of side effects. Those range from mild ones such as fever and swelling at the injection site to more serious, but rarer, conditions such as inflammation of the heart tissues and multisystem inflammatory syndrome (MIS-C), a condition that can cause inflammation in many parts of the body.
Both vaccines were relatively safe and did not generate more adverse effects among children than among adults, although the committee members paid close attention to the risk of myocarditis, an inflammation of the heart tissues that has been reported among young adult males ages 16 to 25 years old. The CDC’s vaccine side effects database did not reveal a higher rate of the condition among younger children.
If the CDC recommends the vaccines for this youngest age group, interested parents will likely have to make a challenging decision about which shot their youngsters will receive. Moderna’s two-dose regimen could be more convenient and mean fewer office or pharmacy visits, compared to Pfizer-BioNTech’s three-dose schedule. It would also take a much shorter amount of time for kids to become fully vaccinated. On the other hand, Pfizer-BioNTech’s three doses appear to provide higher levels of virus-fighting antibodies.
Committee member Dr. Paul Offit, director of Children’s Hospital of Philadelphia’s Vaccine Education Center, was concerned by Pfizer-BioNTech’s “surprisingly poor” vaccine efficacy after two doses. He and other panelists worried that parents won’t realize their children aren’t well protected until after their third shots—especially since kids in the same age group only need two doses of Moderna.
Ultimately, additional doses may become necessary for all children, given that the vaccines currently in use were designed to target the original SARS-CoV-2 virus. That virus has since been replaced by waves of different variants; Omicron, in particular, is better able to evade the immunity produced by the vaccines than past variants. That’s why the FDA and CDC now recommend that all adults receive at least one booster after their initial two-dose vaccination with either Pfizer-BioNTech or Moderna’s shots, in order to push waning levels of virus-fighting antibodies back up to levels that can protect against infection and severe disease.
While the committee was not tasked with evaluating the need for additional doses at this meeting, the same experts will convene again on June 28 to discuss boosters and future COVID-19 vaccination plans. They’ll also review data related to new vaccines developed to target Omicron specifically.
“I think Omicron has brought us to the point where we need to redefine what the primary series of vaccination against COVID-19 should be,” says Dr. Kristin Moffitt, an infectious disease specialist at Boston Children’s Hospital (who does not serve on the FDA committee). “We are in completely uncharted territory and in a very dynamic situation, since the virus and its evolution is really what is driving the bus here.”
It’s possible, for example, that by the fall, health officials may have enough data from newer, Omicron-specific vaccines to decide that everyone—including children—should receive at least one dose of those updated vaccines to remain protected during the winter season. That decision will also depend on longer term data from the ongoing pediatric studies that both Pfizer-BioNTech and Moderna are continuing to collect on how long protection against Omicron lasts with their current vaccine formulations, which in children have only been studied for a couple of months at most. “The question for parents is, will the Pfizer-BioNTech vaccine with its three doses protect kids all the way through the fall and winter so they won’t need another booster, v kids who received two doses of Moderna and may need an additional dose before the fall and winter season?” says Dr. Bonnie Maldonado, who chairs the committee on infectious diseases for the American Academy of Pediatrics and is chief of infectious diseases in pediatrics at Stanford School of Medicine. “We don’t know the answer to that yet. At this point, we can say that both vaccines are safe and effective in protecting children against COVID-19 disease, and that parents will now have a choice, which is helpful.”