COVID-19 vaccine for kids: How young can we go?

While the mRNA vaccines currently available on the market have gained regulatory nods* for use in children aged 5 or 6 years old**, Moderna’s mRNA-1273 vaccine is setting a “new low” by showing that two 25 μg doses of the vaccine induce a robust immune response in infants/children as young as 6 months to <6 years of age, according to the latest data from the KidCOVE study.

At 1 month after the second dose, the study met its primary endpoint with strong neutralizing antibody levels induced, similar to the response seen in adults — a benchmark used for gauging the potential efficacy of vaccine in the younger population.

Taking the antibody response of vaccinated young adults (aged 18–25 years) in the phase III COVE study as comparator, the geometric mean ratio (GMR) of neutralizing antibody induced was 1.3 (95 percent confidence interval [Cl], 1.1–1.5) and 1.0 (95 percent Cl, 0.9–1.2) for the age groups of 6 months to <2 years and 2 to <6 years, respectively. This, according to the researchers, indicates that the potential protective benefit of mRNA-1273 conferred to young adults also extends to infants as young as 6 months old.

The 25 μg vaccine dose used in this very young paediatric population was one-quarter of that used for adults.

So far, children younger than 5 years old are the only age group who cannot get vaccinated against SARS-CoV-2. The BNT162b2 vaccine has been approved for children aged 5 and above in the US. While the mRNA-1273 vaccine has yet to be FDA-approved for young children, it has gotten the green light for use in children aged 6 to 11 years in the European Union, Canada, and Australia.

“We believe these latest results from the KidCOVE study are good news for parents of children under 6 years of age. We now have clinical data on the performance of our vaccine from infants 6 months of age through older adults,” said Moderna CEO Stephane Bancel in a press release.

Shifting priority

During early periods of the pandemic, many believed that children are less likely to develop severe disease from SARS-CoV-2 infection and even questioned the need to vaccinate children.

However, with emerging variants — in particular the Omicron wave which has caused a surge in hospitalizations of infected children and adolescents — vaccination of the paediatric population can no longer be ignored.    

“As a pediatrician who has studied the effect of respiratory viral infections in children for many years, I had difficulty reconciling data from early in the COVID-19 pandemic suggesting that the virus largely spared the paediatric population,” commented Dr Kathryn Edwards from Vanderbilt University Medical Center, Nashville, Tennessee, US, in an editorial. [N Engl J Med 2022;386:789-790]

“As time passed, the negative consequences of the pandemic on children became apparent, with hospitalizations and deaths reported,” she stated.

Based on a study by the US CDC, the peak rates of COVID-19-related hospitalizations among children and adolescents were fourfold higher during the Omicron wave than the Delta wave in the US. [MMWR Morb Mortal Wkly Rep 2022;71:271-278]

How safe is it?

The phase II/III KidCOVE study involved 11,700 paediatric participants under 12 years — of which ~4,200 children were aged 2 to <6 years and ~2,500 were aged 6 months to <2 years. They were randomized to receive either two 25-µg doses of the mRNA-1273 vaccine or saline placebo, given 28 days apart.

As the researchers reported, the vaccines was generally well tolerated in this young population, with a safety profile that was largely consistent with children above 6 years of age and the adult population. Most of the adverse events (AEs) were mild or moderate, and more commonly occurred after the second dose. 

Among the children who received mRNA-1273, fever (>38°C) was reported in 17.0 percent and 14.6 percent of the children in the age groups of 6 months to <2 years and age 2 to <6 years, respectively. High fever (>40°C) was rare, occurring in 0.2 percent of children in each age group.

There were no reports of deaths, myocarditis/pericarditis, or multisystem inflammatory syndrome in children (MIS-C).  

The vaccine efficacy stood at 43.7 percent for children aged 6 months to 2 years and 37.5 percent for children aged 2 to <6 years. While these values appeared relatively low, the findings were “consistent with adult observational data” in face of the Omicron wave, according to the investigators, who also noted that the efficacy reached statistical significance.

As none of the COVID-19 cases became severely ill, no estimates can be drawn on the vaccine efficacy against severe disease.