(CNN)A month after the US Food and Drug Administration delayed key steps toward authorizing Covid-19 vaccines for children under 5, many parents are more eager for the shots than ever.
Dr. Daniel Leonard, a pediatric hospitalist who is working on the Pfizer/BioNTech vaccine trial for these kids, said people are driving in from several states away to take part.
“We’re here in south central Nebraska, and while many may not think that this would be the epicenter of scientific progress, the influx that I’ve had with people from Colorado, Minnesota, Wisconsin, Iowa — some driving eight or nine hours each way overnight to participate in the study,” he said. “They are dedicated.”
About 18 million US children under 5 are still not eligible for the protection of a Covid-19 vaccine. Children are less likely than adults to be hospitalized or to die from Covid-19, but at least 400 children age 4 and younger have died from Covid-19, according to the US Centers for Disease Control and Prevention.
Experts say the wait for a vaccine may not be much longer.
Moderna has said that it expects to report trial data in children 2 to 5 years of age in March, and it may seek sign off from the FDA “if the data is supportive and subject to regulatory consultation.” Moderna’s Covid-19 vaccine is currently authorized in the US only for adults.
Pfizer CEO Albert Bourla said Sunday that he expects to have a vaccine for children 6 months to 4 years old “potentially in May, if it works.”
“And we will be ready with manufacturing,” Bourla added on CBS’ “Face the Nation.” Pfizer’s Covid-19 vaccine is already authorized for people as young as 5.
Johnson & Johnson, which makes the other Covid-19 vaccine authorized in the United States, has a late-stage trial of a vaccine for 12- to 17-year-olds but nothing for this younger group.
Waiting for more data
For a while, it had appeared the US would have a vaccine for children under 5 early in the first months of 2022.
Initially, the Pfizer and BioNTech vaccine for this age group was being tested with just two doses, but the results weren’t what scientists had hoped for and the companies said they would test a third dose. But at the request of the FDA, the companies submitted a request for an emergency use authorization of two doses of the vaccine and said they would continue to test a third doses as the two doses moved through the regulatory process.
n mid-February, the plan changed again. Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said the agency needed to see data from an ongoing trial of a third vaccine dose in these younger children in order to move forward with emergency use authorization. A February 15 meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee was delayed.
Families would have to wait for the third-dose data after all.
“The immunogenicity analysis really showed that the immune response really wasn’t where it should be,” Dr. William Towner, who leads the Clinician Investigator Program for the Southern California Permanente Medical Group, said of the vaccine trials. “I think the data is pretty strong that for children, this will be a three-dose series.”
Two doses didn’t seem to do the trick, agreed Dr. James Versalovic, the pathologist-in-chief at Texas Children’s Hospital, where some Pfizer and Moderna pediatric trials are under way. “The data just weren’t as robust as we had hoped for in terms of immune response,” particularly with children in the 2 to 4 range.
Scientists working on the littlest kid trials have the benefit of observing what happens with other age groups. After seeing breakthrough infections in 2021, Versalovic said, scientists learned quickly that adults and adolescents needed booster doses.
“Taking these lessons to heart, we just pivoted in late December and just kept going forth full-tilt with a third dose and following these children during the trials,” he said. Children who have gotten a third dose need to be followed for at least two months before the data can be submitted to the FDA.
Investigators across the country confirmed that they are working as quickly and as carefully as they can to gather the data. Bourla said Sunday that the company should have data on its three-dose vaccine trial for this age group by April.
“The studies must be done correctly, and if it takes a bit longer, that’s OK; let’s do it right,” said Dr. Sharon Nachman, a pediatric infectious disease specialist at Stony Brook University who has been working on the Pfizer trials. “I think they need to be careful assessing what the immune response is. How long does it last? And really, what did that third dose mean?”
Another Pfizer investigator, Dr. Jennifer Nayak, a pediatric infectious disease specialist who is affiliated with Strong Memorial Hospital of the University of Rochester Medical Center, said it makes more sense to evaluate all the data rather than some of it.
“Really, what it comes down to is trying to get as much data as we can and be as careful as we can and make the best recommendations,” Nayak said.
Dr. Jonathan Hand, an infectious disease specialist working on the Pfizer trial in New Orleans with Ochsner Medical Center, said that all the careful work that goes into these trials should reassure parents once a vaccine is made available.
“Data integrity and patient safety are so critical to this process,” he said.
The good news, investigators say, is that they haven’t seen any safety issues.
“The data is quite clear that there’s good safety. It’s not all published and it’s not all public, but the vaccines are safe,” said Dr. Janet Englund, who is working on the Pfizer trial at Seattle Children’s.
Keeping up with variants
The biggest questions that remain are exactly how protective the vaccines are, what the right vaccine schedule is and what the right dose is.
The results to be released in the coming weeks and months should answer that question.
“We’ve always said that the number one goal is to prevent hospitalization, but families would like them to prevent transmission in the household, particularly if they have people in the household that are at risk like the elderly,” Englund said.
One challenge is that the vaccines are being tested in what scientists call a “different viral period.” The Covid-19 vaccines were developed off the initial variant and tested during the Delta surge. Now, researchers are collecting data on the third shot while the Omicron variant is the most dominant.
“Omicron kind of changed all bets,” Towner said. “Omicron was highly mutated and obviously spread very quickly.”
If it’s authorized, there’s a chance that little kids could get a vaccine on a different schedule than what adults and adolescents get. Rather than wait four or five months before a third dose, like with older ages, they could get a third shot as soon as two months after the second shot.
“Children are not simply small adults. They are growing and developing throughout childhood,” Versalovic said. That affects how the vaccines work.
Another Pfizer investigator, Dr. Yvonne Maldonado, chief of the Division of Infectious Diseases in the Department of Pediatrics at Stanford Medicine and a committee chair with the American Academy of Pediatrics, said they should know what they have soon. “I do think we are getting closer to some answers,” she said.
As with any vaccine trial, Dr. Claire Boogaard, a pediatric infectious disease specialist and medical director of the Covid-19 vaccine program at Children’s National in Washington, said it is important to remember that scientists are still learning about the disease as they look for ways to fight it. With variants, a lot can change quickly.
“We want to encourage everyone to just be flexible, because that’s actually what the science requires,” Boogaard said. “The reality is, there are a lot of variables at play.”
All the scientists working on these trials said they understand parents’ desire to protect their children. When the FDA postponed the meeting of its vaccine advisers, Marks said he understood parents’ frustration.
In the meantime, he urged parents to keep taking Covid-19 precautions: Make sure everyone around the child is vaccinated and rely on “masking procedures,” although that’ has become more difficult as mask mandates fall.
As soon as the FDA gets the necessary data to make a decision about vaccines for younger children, Marks said, it will proceed “very rapidly.”