A study of Moderna’s COVID vaccine in children aged 6 months to 5 years

In a recently published study in the New England Journal of Medicineresearchers presented the results of the ongoing KidCOVE study in the United States (US).

Study: Evaluation of mRNA-1273 vaccine in children aged 6 months to 5 years. Image source: myboys.me / Shutterstock

background

Messenger ribonucleic acid (mRNA) vaccines for coronavirus disease 2019 (COVID-19), including mRNA-1273, have demonstrated a favorable safety profile and efficacy in adults, adolescents, and older children aged six to eleven years. Therefore, in June 2022, they received an emergency use authorization (EUA) from the US Food and Drug Administration (FDA) for people aged six months to 17 years. The KidCOVE study then evaluated the efficacy, safety and immunogenicity of the mRNA-1273 vaccine in young children aged six months to five years.

Despite loss of vaccine efficacy against some Omicron subvariants, mRNA-1273 vaccination prevents COVID-19-related hospitalizations and deaths. In the US, between October 2020 and September 2021, these incidents exceeded annual flu-related hospitalizations and death rates in children under the age of five. There is an urgent need for a safe and effective vaccine for infants, toddlers and young children.

About the study

In the present study, researchers described the results of an ongoing mRNA-1273 vaccine trial (KidCOVE) in the United States. The team recruited healthy children at 79 and eight sites in the US and Canada between April 2021 and June 2021, respectively. They stratified all eligible children into three age cohorts of 6 to 11 years, 2 to 5 years, and 6 to 23 months.

In the first phase, the 25 mcg and 50 mcg doses of mRNA-1273 vaccine were tested in children aged two to five years and children aged six to 23 months, respectively. The team administered two doses of the mRNA-1273 vaccine or a placebo with saline intramuscularly, 28 days apart. They selected a 25 mcg dose to evaluate in all children for Phase II of the study based on a review of its safety and immunogenicity. In phase II, the team first randomly assigned children aged six to five months in a 3:1 ratio to two 25 μg doses of mRNA-1273 or placebo administered 28 days apart.

The team monitored and recorded local and systemic side effects within seven days of each vaccination in the study phases. The primary objective of the study was to determine the safety and reactogenicity of mRNA-1273. The secondary objective was to determine the incidence of COVID-19 in recipients of the vaccine or placebo.

study results

The study population included 239 children, of whom 224 and 150 belonged to the cohorts aged 2 to 5 years and 6 to 23 months, respectively. In trial phase II, the researchers analyzed 3,040 and 1,762 children in the age groups two to five years and six to 23 months, respectively. While these children received two 25 μg doses of mRNA-1273, 1,008 and 593 children of the same age group were randomly assigned to receive the placebo. The study median follow-up times after the second vaccination were 71 and 68 days in the age groups 2 to 5 years and 6 to 23 months, respectively.

A 25 mcg double-dose regimen of mRNA-1273 in children ages six months to five years elicited similar immune responses to higher doses of this vaccine in older children, adolescents and adults. In addition, the effectiveness of the vaccine against COVID-19 was lower than in previous mRNA-1273 studies conducted before Omicron came out. Furthermore, in phase II of this study, this dosage elicited transient, mild to moderate reactogenicity in both age cohorts.

Almost 23% of children in both age cohorts developed a fever after either mRNA-1273 vaccination. Some children developed a grade 4 fever (>40.0 °C). However, no serious adverse events such as myocarditis, pericarditis or death occurred. Overall, there were no security issues before or during the analysis cut-off date. Finally, mRNA-1273 vaccination elicited adequate serum levels of neutralizing antibodies in these younger children, similar to those that elicited two 100 μg doses of mRNA-1273 in adults.

In addition, the mRNA-1273 vaccine elicited an immune response that met non-inferiority criteria for both age cohorts. At day 57, the geometric mean neutralizing antibody concentrations were 1410 and 1781 in children aged 2 to 5 years and 6 to 23 months, respectively. In young adults who received a 100 μg dose of mRNA-1273, antibody geometric mean values ​​were lower, reaching only 1,391.

Conclusions

During the period of SARS-CoV-2 omicron dominance in the US, primary immunization with 25 μg of mRNA-1273 was beneficial in young children. Its effectiveness against COVID-19 was 36.8% and 50.6% in children aged 2 to 5 and 6 to 23 months, respectively. Fortunately, clinical trials evaluating the long-term effectiveness of mRNA-1273 will continue even after its approval. All active and passive safety monitors will continue to detect new safety signals related to post-approval use of mRNA-1273.