Which coronavirus vaccine will work in younger children?

WASHINGTON — For the past 10 months, as tens of millions of children and teens received the Pfizer-BioNTech vaccine, the companies’ arch-rival Moderna sat on the sidelines, its shot limited. to adults.

But Moderna may now be on the verge of returning at a critical moment in the national vaccination campaign. The company is expected to send federal authorities initial data this week on the effectiveness of its coronavirus vaccine for the nation’s youngest children.

About 18 million children under age 5 are the only Americans not yet eligible for vaccination. And although adoption for older children has been slow, many parents are still eagerly awaiting the chance to protect their babies, toddlers and preschoolers.

Moderna is squaring off with Pfizer-BioNTech for the opportunity to vaccinate this group, hoping it has found what some scientists call the “Goldilocks” dose: strong enough to provide lasting protection, but not so strong that it causes widespread spread of worrisome side effects, such as high fever.

Moderna opted for a two-dose regimen at a quarter of the strength of its adult dose for children under 6 years old. Pfizer is expected to seek approval next month for a three-dose regimen for children under 5, with doses one-tenth as strong as those for people aged 12 and over.

Moderna is also expected to soon release data from its clinical trial on the following age group: children aged 6 to 11 years.

Dr. Yvonne Maldonado, Stanford professor of pediatric infectious diseases and principal investigator at the Stanford Site of Pfizer’s Pediatric Vaccine Trials, said new data from Moderna and BioNTech in the coming weeks will offer critical insight into the disease. effectiveness of their pediatric injections. She said the researchers were watching carefully to see if the higher doses of Moderna “resulted in more robust immune responses” than the Pfizer injections elicited in young children.

A series of new studies raising questions about how long Pfizer’s lower doses protect school-aged children has sparked interest from 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 Board, said he thinks Pfizer may have chosen too low a dose for children under 5 to 11 years” in the understandable priority to maximize safety.

To date, Pfizer has been the only player in vaccinating young Americans, gaining approval 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 applied for approval to vaccinate teenagers last June, but the FDA delayed reviewing the application due to concerns about the risk of myocarditis, a condition involving inflammation of the heart linked to both injections of Moderna and Pfizer.

In the United States, more than 22 million people under the age of 18 are now fully immunized with the Pfizer vaccine, but uptake has leveled off. Only about one in four children aged 5 to 11 are fully immunized, for example, even though injections have been offered to this group for more than four months.

But there is still a demand to protect the youngest children as more countries come unmasked, more parents return to workplaces and the summer travel season approaches.

Compared to adults, “there is no doubt 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 Harvard TH Chan School. of Public Health and a member of an advisory panel to the Food and Drug Administration.

“But it will benefit some people,” he said. “It will save lives.” According to the Centers for Disease Control and Prevention, 336 children in the United States under the age of 5 have died from Covid since the start of the pandemic.

Hopes that younger children would soon be covered surged last month after regulators pressed Pfizer-BioNTech to submit preliminary results from its three-dose trial. The FDA wanted to launch the vaccination campaign with two doses pending final results on three.

But that effort crumbled when new data from Pfizer that encompassed more of the Omicron push convincingly showed that two doses did not adequately protect against symptomatic infection.

Now, more detailed results from the Pfizer and Moderna trials are materializing around the same time. And while neither company yet knows whether its vaccines will prove effective enough for the younger age group, both say their research shows they are safe.

“We haven’t seen anything untoward so far, so we’re confident in the safety profile,” Moderna Chief Medical Officer Dr. Paul Burton said in an interview.

Amy Rose, spokeswoman for Pfizer, said that after extensive research, Pfizer-BioNTech chose the “safest and most tolerable dose” for young children. The companies said they hoped a three-shot regimen would provide strong protection for children under age 5. Pfizer is testing a 10-microgram dose for children ages 5 to 11, one-third of adults and adolescents. dosing; and 3 micrograms for children under 5 years old.

Moderna offers a significantly higher dosage than Pfizer in all three pediatric age groups: 100 micrograms, the full adult dose, for ages 12 to 17; 50 micrograms for children 6 to 11 years old and 25 micrograms for children under 6 years old. Regulators are seen as likely to review company data for all three age groups simultaneously.

“We really support these doses,” Dr. Burton said. Although federal officials say the potency of Pfizer’s and Moderna’s vaccines decreases over time, some studies in adults have suggested Moderna’s protection lasts longer. “I think it depends on the dose,” Dr. Burton said.

He said early results showed a 50-microgram dose of Moderna elicited a “robust immune response” in children aged 6 to 11. Although the total number of infections is low, the researchers hope the trial will help reveal how well the vaccine prevents disease, not just how high it boosts antibody levels.

Dr. Philip Krause, who recently retired as senior vaccine regulator at the FDA, said the agency spent a lot of time last year worrying about the safety of Moderna’s vaccine for patients. under 18, with some studies showing a higher risk of myocarditis from the company’s vaccine. than at Pfizer.

“The question is always, what is the dose that elicits an immune response that we think is likely to be protective?” he said. “You can’t actually test for the rate of myocarditis because it’s rare, but you can ask, ‘What are we sacrificing in the immune response by lowering the dose, and do we think that’s important?’ “”

In part because of concerns about myocarditis, the CDC recently encouraged some people 12 or older, especially boys and men between 12 and 39, to wait eight weeks between their first and second Pfizer or Moderna vaccines. . Studies have shown that teenagers and young men are most at risk of developing the side effect.

Dr Burton said overall the research had been reassuring, including recent UK data that showed myocarditis was very rare and generally mild in Pfizer and Moderna beneficiaries.

But Dr Walid F. Gellad, a drug safety expert at the University of Pittsburgh, said it was unclear whether the higher dose of Moderna might increase the risk of myocarditis in young children. The company’s pediatric studies are likely far too small to identify side effect risk, 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 offer children ages 5 to 11. New York State Health Department researchers recently found that protection against infection from two doses waned significantly within weeks.

CDC researchers separately found that during the Omicron wave, the effectiveness of two doses of the Pfizer vaccine against mild forms of the disease in children ages 5 to 11 decreased significantly.

The studies have sparked debate among vaccine experts about whether a higher dose would have been better or whether these children need third doses. Booster injections are now authorized for everyone from the age of 12. Pfizer expects the results of its study of a three-dose regimen for young children next month.

Dr Gellad said it was possible that Pfizer’s dose for children aged 5 to 11 was too low, but scientists could not yet be sure. He said he expected regulators to be particularly careful in considering higher doses for young children given the relatively low risks of them catching Covid now and becoming seriously ill.

Amid all the questions, one thing is clear: the back and forth over which vaccine will be best for young children could discourage adoption.

Alison M. Buttenheim, a behavioral health expert at the University of Pennsylvania, said those considering vaccination find comfort in certainty. Otherwise, “it’s just going to set the stage for saying, ‘I’m going to wait,'” she said. “A lot of people are uncomfortable with the evolution of science.”