The Infuriating Wait for the Youngest-Kids Vaccine

Monserat Ramos, 3, keeps a close eye on the needle as both of her grandparents are vaccinated at a clinic run in Los Angeles. Photo: Francine Orr/Los Angeles Times via Getty Images

Technically, White House COVID czar Jeffrey Zients wasn’t talking about my toddler when he warned last week that the unvaccinated are “looking at a winter of severe illness and death for yourselves, your families, and the hospitals you may soon overwhelm.” A charitable read of the fuller press briefing makes clear that Zients was talking about willfully unvaccinated adults; he spent a good chunk of time encouraging parents to vaccinate kids who are eligible.

But coming on the day when Pfizer announced a setback for its COVID-19 vaccine trial for children under 5, pushing back their eligibility yet again, his words rankled their parents and caregivers. With the expected timeline for FDA approval pushed back yet again to somewhere in the middle of next year, we’re stuck parsing the shifting hospitalization numbers by age for each variant to see if COVID is still considered “mild” for our kids. Apart from the eligible people around them, the only other way to build their “immunity wall” is by getting sick.

Possibly that’s why Joe Biden gave us a special shout-out in his remarks Tuesday. “And for those parents out there who have a child that’s too young to be vaccinated — that is, under the age of 5 — I know this can still be a scary time,” the president said. “But one thing you can and must do while we await vaccines for children under 5: Get yourself fully vaccinated and boosted, as well as those around you — your children, your caregivers, your siblings.”

I’m willing to bet that almost everyone who is worried about COVID and their kid under 5 — a group 24 million strong that spans little babies, furniture-climbing toddlers, and preschoolers — is already on it. In the meantime, we can try to parse what went wrong with the Pfizer trial, which executives initially predicted would report results for these age groups in the fall. (My daughter, as I’ve written, is in an under-5 vaccine trial, but I don’t know anything more than what’s been publicly announced and what I’ve been able to independently report.)

The youngest kids were divided into two groups: 6 months to just under 2 years and 2 to 5 years old. In the Phase 1 trial that started in the spring, the company tested different dosages, from the 30 micrograms adults now get to as little as 3 micrograms, to evaluate both safety and immune response. According to Kathrin Jansen, Pfizer’s head of vaccine research, they decided to move forward to Phase 2 and 3 with the three-microgram dose based on its minimal side effects.

“We have noticed that fever and chills are two of the most important systemic events for decision-making,” she said on Pfizer’s earnings call Friday, apparently referring to parental decision-making about whether to vaccinate their kids. “We decided that the three-microgram dose level given 21 days apart would be most appropriate for moving ahead into Phase 3 as it has acceptable fever profiles in both pediatric populations,” she added. At the same time, Jansen said, they found evidence that the smaller dose created an immune response “about the same or greater” than in older populations.

So far, so good — except that Pfizer was actually announcing that an independent monitoring committee considered the immune response sufficient for the 6-month to 2-year-old population but insufficient for 2- to 5-year-olds. Their solution is to now test a third dose for younger kids before seeking approval in light of booster data for older groups. Frustratingly, because the “age de-escalation” study design goes from older groups to younger groups, Pfizer won’t ask for approval for the youngest children even though the company deemed results for them to be safe and effective.

I’m not the only one to find Pfizer’s entire account perplexing. “So obviously the 3 micrograms dosage was incorrect for 2- to under 5-year-olds,” Dr. Katelyn Jetelina wrote in her newsletter, Your Local Epidemiologist. “But why wasn’t this detected in Phase I ‘dosage finding’ stage?”

In an interview, Dr. Paul Offit, who directs the Vaccine Education Center at the Children’s Hospital of Philadelphia and sits on the FDA’s vaccine advisory committee, agreed: “This typically is worked out in Phase 1.” I asked that question of a Pfizer spokesperson, but they didn’t respond to that part.

Maybe the definition of “fully vaccinated” is destined to change to three shots for everyone, but if Pfizer had figured out its original dosage was inadequate back in the spring, or even after the first kids in the broader trial started getting shots in June, we’d have a lot less waiting for the first shot ahead of us. On the call, Jansen claimed this “is not anticipated to meaningfully change” the plan to seek approval in the second quarter of 2022, but that timeline already was months later than the one laid out in September to report data in October or November, with a request to the FDA presumably to follow. The Pfizer spokesperson responded, “Our timeline was to provide an update by the end of the year, and we shared an update last week providing the update we had available.” Okay.

Pfizer has not yet made a submission to the FDA to amend its trial, so it’s unclear when this third dose will be administered. Meanwhile, Moderna might have data from its Phase 2 and 3 trials for the youngest kids in mid-January, but its pediatric trials are stuck in a holding pattern. The company has said it won’t even ask the FDA for emergency authorization of its vaccine for 6- to 11-year-olds until the FDA has finished reviewing whether its vaccine for teenagers poses unacceptable risks of myocarditis (heart inflammation), which might not happen until mid-January. Johnson & Johnson hasn’t even announced a trial for kids under 12.

Offit told me it’s too soon to say much about Omicron but pointed out that, overall, children now account for a larger proportion of cases; without the same levels of protection as the vaccinated, “they’re more susceptible.”

It’s hard not to feel that both vaccine makers and the FDA, which asked them to expand their trials last summer, could be approaching this with a lot more urgency. When New York Times columnist Michelle Goldberg looked into the holdup for a vaccine for 5- to 11-year-olds last August, Stanford professor and lead Pfizer pediatric vaccine investigator Dr. Yvonne Maldonado told her she suspected the FDA “wanted to allay a lot of the fears that we’re hearing from different people who are worried about these vaccines and kids.” That age group was approved at the end of October. Offit, from his perch on the FDA advisory committee, strongly disagreed that anything like that has affected the overall timeline for the pediatric vaccines. “I don’t think the anti-vaccine people in any way are determining the way this is being done,” he said.

“We need a vaccine for children, including younger children,” he continued. “They still can be infected and have severe and occasionally fatal illness. If we can prevent that safely, then we should prevent it.” In the meantime, we wait.