When clinical trials began last year to test the safety and efficacy of COVID-19 vaccines, their focus was on adults, who were deemed most susceptible to severe illness and death if they contracted the SARS CoV-2 virus. Since then, three vaccines have received emergency use authorization from the U.S. Food and Drug Administration (FDA) and millions of doses have been administered to Americans age 16 and over.
The testing threshold is getting younger. On April 9, Pfizer and BioNTech submitted data based on recently completed clinical trials for ages 12 to 15, expressing hope that the FDA will authorize this age group to be vaccinated before the next school year begins in late summer. Onyema Ogbuagu, MBBCh, associate professor of medicine, led Yale’s component of the 12-to-15 trial, as he had done in 2020 for the Pfizer BioNTech adult trial. He says returning to school is just one of several important considerations. “If kids make up nearly 30 percent of the population and we can vaccinate them with a low margin of error, that puts us on an easier path toward herd immunity,” Ogbuagu says.
The effort to evaluate COVID-19 vaccines in even younger children is now moving forward. Inci Yildirim, MD, PhD, associate professor of pediatrics (infectious diseases) at Yale School of Medicine, will lead Yale’s component of Moderna’s clinical trial of a vaccine for children 6 months to 12 years of age. Called KidCOVE, the phase 2/3 trial is being conducted at approximately 90 sites across the U.S. and Canada and will include 6,750 children.
Yildirim, a vaccinologist, says evidence suggests that even beyond its contribution to herd immunity, vaccinating young children could protect their own health more than people assumed when the pandemic began. “As the pandemic evolved we have learned many things that we didn’t know initially,” says Yildirim. “We learned in fact that children can get infected and develop severe disease requiring intensive care unit admissions. We have seen children transmitting SARS-CoV-2 to other children and adults in summer camp or family gatherings.”
There also is a concern that so-called “long COVID” may have lasting or recurring effects for the children themselves, as Ogbuagu explains. “We know that people have had long COVID symptoms even if they weren’t hospitalized and these symptoms can persist for longer than a typical illness,” he says. It is yet another reason to want very young children to be vaccinated safely and effectively.
Testing children’s vaccines is more complicated
Yildirim says trials for children younger than 12 will be far more complicated than adult trials like one for Moderna in which she was an investigator last year, and will take more time to complete. “A clinical trial for a children’s COVID-19 vaccine requires the consideration of many additional factors,” she explains. “Children are not little adults. As children grow and develop, their immune system grows and develops. A 16-month-old is not the same as a 16-year-old. They are both children, but their capacity to respond to the vaccines is not the same.”
The protocol Yildirim will follow was developed in collaboration with the National Institute of Allergy and Infectious Diseases and Moderna. It consists of two parts: the first, which seeks to determine a safe dose of the antigen; and the second, to test whether the dose is effective. This is called an “age de-escalation/dose escalation” study. Participants are placed in three groups: 6 to 12 years old, 2 to 6 years old, and 6 months to 2 years old.
“We have a dose that we would start in the older group, and once we show that that dose is safe in that age group, we would go down to the younger age group,” says Yildirim. “Doses begin at the lowest, safest level, and then are increased to determine if a larger dose is more effective, or if the lower dose will provide an adequate response. Throughout, there are multiple safety checkpoints where results will be examined, more than there would be in an adult clinical trial.”
The other vaccines that children routinely receive also influence how the COVID-19 trial will be conducted. “The pediatric study will be more complicated because of scheduling and will take longer than adult studies,” says Yildirim. “We have to make sure in introducing a vaccine to younger kids that it is safe, that the vaccine is not interacting with other vaccines, and it is not reducing the impact of other vaccines.”
Adult vaccine success
While mask wearing, handwashing, and social distancing remain essential, including for people who have been vaccinated, the development of COVID-19 vaccines has been an amazing feat, Yildirim says. “During the urgency of the pandemic we used the skills and scientific discoveries we had been accumulating over the last decade or two to develop a vaccine within an incredibly short time. The initial adult trial was the first time a human being received that vaccine. And within nine months, I got the same vaccine in my arm with many other health care workers.” Yildirim compares that speed with the nearly 50 years it took to have a safe and effective vaccine for polio, and says it sets the stage for new vaccines to guard against other diseases. “I am very hopeful we will have safe and effective vaccines for many other infectious pathogens in the near future,” she says.
The Yale Center for Clinical Investigation, supported by the federal Clinical and Translational Science Awards (CTSA) program, oversees and provides resources for clinical trials.