In the COVID-19 pandemic, new variants have necessitated the adaptation of vaccines to maintain their efficacy. Moderna’s mRNA-1273 vaccine, branded as SPIKEVAX, has been at the forefront of this battle, especially in pediatric populations. This study focuses on the vaccine’s safety, efficacy, and immune response in children aged 6 months to 11 years, particularly against the delta and omicron variants. With the introduction of the modified mRNA-1273.214 version, there is an advancement in the fight against the evolving SARS-CoV-2 strains.

During the trial period, when the delta variant was prevalent, SPIKEVAX showed an 88% efficacy rate in preventing COVID-19 in children aged 6 to 11. However, the efficacy dropped with the rise of the omicron variant, marking 45.8% in the 6 to 23 months age group and 39.6% in the 2 to 5 years age group. The modified mRNA-1273.214 variant demonstrated a robust immune response against the BA.1 and D614G strains, irrespective of it being administered as a 2-dose primary series or as a booster.

“These findings are among the first to demonstrate the safety and inferred effectiveness based on immunobinding of a variant-containing COVID-19 vaccine in pediatric populations and support a 2-dose schedule for previously unvaccinated children with an additional dose when the formulation is successively updated,” according to investigators. “Further studies are needed to assess the effectiveness and durability of variant-containing COVID-19 vaccines in children.”

The study was conducted as an open-label, non-randomized phase 3 trial across 24 U.S. sites, engaging children aged 6 months to 5 years. Excluding those with recent SARS-CoV-2 infections or vaccinations other than mRNA-1273, the study aimed to evaluate the modified mRNA-1273.214 vaccine’s safety, reactogenicity, and presumed efficacy.

179 participants received the primary series of the mRNA-1273.214 vaccine, and 539 received the booster dose. The vaccine’s safety profile was consistent with the initial mRNA-1273 series, with no new safety concerns reported. The immune response was notably stronger against the omicron BA.1 variant post-vaccination.

“A previous study evaluating mRNA-1273 in children aged 6 months to 11 years demonstrated that a single dose is ineffective in individuals without pre-existing immunity, and two doses are required to induce adequate immune response,” according to investigators.” As COVID-19 transitions to an endemic disease, it remains to be determined at what age most individuals would have evidence of previous SARS-CoV-2 infection, which would then dictate changes to the COVID-19 immunization schedule.”

Between June 21, 2022, and December 5, 2022, 179 participants received one or more doses of the mRNA-1273.214 vaccine as part of the primary series, and 539 received the booster dose. The safety profile observed within 28 days after any dose administration matched that of the initial mRNA-1273 series for this age group, with no new safety concerns or serious adverse events reported.

The study is limited by its open-label design and lack of a contemporary control group due to COVID-19 vaccination guidelines, which showed the bivalent vaccine-elicited immune responses in individuals regardless of previous exposure. Initial results revealed higher immunogenic responses in those previously exposed to SARS-CoV-2. The new mRNA-1273.214 vaccine induced higher antibody levels against the BA.1 variant compared to the original mRNA-1273 vaccine in those not previously exposed, supporting the use of variant-adapted vaccines as recommended by the FDA and CDC for the omicron XBB.1.5 variant. The findings suggest that both vaccine-naive and previously vaccinated children would benefit from the current variant-matched vaccine.

Despite a decrease in efficacy from delta to omicron, the modified vaccine elicited strong immune responses as both a primary series and a booster, with a consistent safety profile. Conducted across 24 US sites, findings support using a 2-dose regimen for unvaccinated children and highlight the ongoing need to adapt COVID-19 vaccines to combat evolving virus strains.

Reference

Dixit A, Bennett R, Ali K, Griffin C, Clifford R, et. al. Interim Safety and Immunogenicity of COVID-19 Omicron BA.1 Variant-Containing Vaccine in Children in the USA: an Open-Label Non-Randomized Phase 3 Trial. The Lancet Infectious Disease. Published March 19, 2024. Accessed March 20, 2024. doi: https://doi.org/10.1016/S1473-3099(24)00101-4