WASHINGTON — Over the past 10 months, as tens of millions of children and teenagers received the Pfizer-BioNTech vaccine, the companies’ main rival, Moderna, sat on the sidelines, its shot limited to adults.
But Moderna may now be poised for a comeback at a critical juncture in the nation’s vaccination campaign. The company is expected to send federal officials initial data this week on how well its coronavirus vaccine works for the nation’s youngest children.
About 18 million children under the age of 5 are the only Americans not yet eligible for vaccination. And while uptake for older children has been slow, many parents are still anxiously awaiting the chance to protect their babies, toddlers and preschoolers.
Moderna is going head-to-head with Pfizer-BioNTech for the opportunity to vaccinate this group, hoping it has found what some scientists are calling the “Goldilocks” dose: strong enough to offer lasting protection, but not so strong that it causes widespread worrisome side effects, such as high fevers.
Moderna has opted for a regimen of two doses at a quarter the strength of its adult dose for children under 6. Pfizer is expected to seek authorization next month for a three-shot regimen for children under 5, with doses one-tenth as strong as those for people aged 12 and up.
Moderna is also expected to release data soon from its clinical trial on the next age group up: children aged 6 to 11.
Dr. Yvonne Maldonado, a Stanford professor of pediatric infectious diseases and a lead investigator at the Stanford site of Pfizer’s pediatric vaccine trials, said new data from both Moderna and BioNTech in the coming weeks will offer critical insight into the effectiveness of their pediatric shots. She said researchers are watching carefully to see if Moderna’s stronger doses “result in more robust immune responses” than Pfizer’s shots have elicited in young children.
A series of new studies raising questions about how long Pfizer’s lower doses protect elementary-school-age children has piqued interest among federal scientists and vaccine experts in Moderna’s choices.
Dr. Ofer Levy, a pediatric expert at Harvard Medical School and a member of the Food and Drug Administration’s independent vaccine advisory committee, said he thought Pfizer might have selected too low a dose for 5- to 11-year-olds “in the understandable priority to maximize safety.”
To date, Pfizer has been the only player in vaccinating younger Americans, winning authorization to vaccinate 12- to 15-year-olds last May, followed by 5- to 11-year-olds in October. Its authorization for adults also covers 16- and 17-year-olds.
Moderna sought authorization to vaccinate teenagers last June, but the F.D.A. delayed considering the request because of concerns about the risk of myocarditis, a condition involving inflammation of the heart that has been tied to both the Moderna and the Pfizer shots.
More than 22 million people in the United States under 18 are now fully vaccinated with the Pfizer vaccine, but uptake has been leveling off. Only roughly one in four children ages 5 to 11 are fully vaccinated, for example, even though shots have been offered to that group for more than four months.
But there is still a demand to protect the youngest children as more of the country unmasks, more parents return to workplaces and the summer travel season approaches.
Compared with adults, “there is no question that in children the benefit of an effective vaccine is less, because fewer get really sick,” said Dr. Eric Rubin, an infectious disease expert at the Harvard T.H. Chan School of Public Health and a member of an advisory panel to the Food and Drug Administration.
“But it will benefit some individuals,” he said. “It will save some lives.” According to the Centers for Disease Control and Prevention, 336 children in the United States under the age of 5 have died of Covid since the start of the pandemic.
Hopes that the youngest children would soon be covered surged last month after regulators pressed Pfizer-BioNTech to submit preliminary results from its three-dose trial. The F.D.A. wanted to get the vaccination campaign underway with two doses while awaiting final results on three.
But that effort collapsed when new data from Pfizer that encompassed more of the Omicron surge showed convincingly that two doses failed to protect adequately against symptomatic infection.
Now, more detailed results from Pfizer’s and Moderna’s trials are materializing at roughly the same time. And while neither company knows yet whether its vaccines will prove effective enough for the youngest age group, but both say their research shows they are safe.
“We have not seen anything untoward right now, so we feel confident in the safety profile,” Dr. Paul Burton, Moderna’s chief medical officer, said in an interview.
Amy Rose, Pfizer’s spokeswoman, has said that after careful research, Pfizer-BioNTech chose the “safest and most tolerable dose” for young children. The companies have said they are hopeful that a three-shot regimen will provide strong protection for children under the age of 5. Pfizer is testing a 10-microgram dose for 5- to 11-year-olds, a third of the adult and teenage dosing; and 3 micrograms for children under 5.
Moderna is proposing substantially higher dosing than Pfizer in all three pediatric age groups: 100 micrograms, the full adult dose, for those ages 12 to 17; 50 micrograms in children 6 to 11, and 25 micrograms in those under 6. Regulators are considered likely to review the firm’s data for all three age groups simultaneously.
“We really stand behind those doses,” Dr. Burton said. Although federal officials say both Pfizer and Moderna’s vaccines wane in potency over time, some studies of adults have suggested that Moderna’s protection holds up longer. “I think it comes down to dose,” Dr. Burton said.
He said initial results showed a 50-microgram Moderna dose prompted a “robust immune response” in children 6 to 11. While the overall number of infections was small, researchers hope that trial will help reveal how well the vaccine prevents illness, not just how high it boosts antibody levels.
Dr. Philip Krause, who recently retired as a senior vaccine regulator at the F.D.A., said the agency spent significant time last year worrying about the safety of Moderna’s vaccine for those under 18, with some studies showing a higher risk of myocarditis from the company’s shot than from Pfizer’s.
“The question is always: What is the dose that gives rise to an immune response that we think is likely to be protective?” he said. “You couldn’t actually test to figure out the rate of myocarditis since it’s rare, but you could ask, ‘What are we sacrificing in immune response by lowering the dose, and do we think that’s important?’”
Partly because of concerns about myocarditis, the C.D.C. recently encouraged some people 12 or older, particularly boys and men between 12 and 39, to wait eight weeks between their first and second Pfizer or Moderna shots. Studies have shown that teenage boys and young men are most at risk of developing the side effect.
Dr. Burton said that overall the research had proved reassuring, including recent British data that showed myocarditis was very rare and typically mild in both Pfizer and Moderna recipients.
But Dr. Walid F. Gellad, a drug safety expert at the University of Pittsburgh, said it remained unclear whether Moderna’s higher dosing might elevate the risk of myocarditis in young children. The company’s pediatric studies are most likely much too small to identify the risk of the side effect, he and other experts said.
Moderna’s new push also comes after several studies raised questions about the protection that two doses of Pfizer-BioNTech’s vaccine provide for children 5 to 11. Researchers in New York State’s health department recently found that protection against infection from two doses faded significantly within weeks.
C.D.C. researchers separately found that during the Omicron wave, the effectiveness of two doses of the Pfizer shot against moderate forms of the disease in children ages 5 to 11 dropped significantly.
The studies have kindled a debate among vaccine experts about whether a stronger dose would have been better or whether those children need third doses. Booster shots are now authorized for everyone 12 and up. Pfizer expects results from its study of a three-dose regimen for the younger children next month.
Dr. Gellad said it was possible the Pfizer dose for 5- to 11-year-olds may have been too weak, but that scientists could not yet be certain. He said he expected regulators would be especially careful in considering higher doses for young children given the comparatively low risks of them catching Covid now and getting severely ill.
Amid all the questions, one thing is clear: The back and forth over which vaccine will be better for young children could discourage uptake.
Alison M. Buttenheim, a behavioral health expert at the University of Pennsylvania, said those considering vaccination found comfort in certainty. Otherwise, “that’s just going to pave the way to say, ‘I’m going to hold off,’” she said. “A lot of people are uncomfortable with evolving science.”