The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the coronaviru2019 (COVID-19) pandemic, has already infected about 207 million people and claimed more than 4.3 million lives worldwide. Scientists opine that mass vaccination is one of the most effective ways to contain the pandemic. Vaccination programs have commenced in many countries, but these have mainly been for adults. The safety, immunogenicity, and efficacy of the vaccines in adolescents are largely unknown. Now, a new study published in the New England Journal of Medicine evaluates the safety and efficacy of the mRNA-1273 vaccine in adolescents (12-17 years of age).
Scientists estimated the incidence of COVID-19 among adolescents, in the period between April 1 and June 11, as being approximately 900 per 100,000 children. The opening of schools may have impacted the rise in the number of cases among children and teenagers. Albeit rare, children can also suffer from serious COVID-19. Statistics show that approximately one-third of hospitalized children needed intensive care, and about 5% required invasive mechanical ventilation.
The mRNA-1273 vaccine was developed by Moderna Inc. and is a liquid nanoparticle dispersion that contains an mRNA that encodes the SARS-CoV-2 S glycoprotein. In several ongoing trials involving adults, this vaccine's safety, immunogenicity, and efficacy have been established. Subsequently, mRNA-1273 received emergency use authorization (EUA) from the Food and Drug Administration (FDA) in December 2020 for use in adults.
A New Study
In the current study, scientists conducted a phase 2-3 trial to evaluate the use of the Moderna vaccine among adolescents. 3,732 participants were randomly assigned in a 2:1 ratio to two groups. The first (treatment) group was to receive the mRNA-1273 vaccine, and the second (control) group was to receive a placebo (saline) 28 days apart. The characteristics of the two groups were generally balanced. The mean age of the participants was 14.3 years; 51% were male, most were White (84%), 88% were not Hispanic, and 93% had a body-mass index of less than 30.
The primary objectives were to evaluate the safety and reactogenicity of the total dose of 200 μg of the vaccine administered in two injections and to infer the efficacy of mRNA-1273 in adolescents by comparing serum antibody responses. Participants maintained an electronic diary where they recorded solicited local and systemic adverse reactions daily for seven days after each injection. A data and safety monitoring board were in charge of conducting periodic unblinded data reviews.
The primary objective was to measure the neutralizing antibody titers with a validated lentivirus pseudovirus (D614G) assay with a 50% inhibitory concentration. The secondary objective was to monitor the incidence of SARS-CoV-2 infection, asymptomatic SARS-CoV-2 infection, and COVID-19 (confirmed by a positive reverse-transcriptase–polymerase-chain-reaction [RT-PCR] test), 14 days after the second injection of the mRNA-1273 or the placebo. The vaccine efficacy was calculated as one minus the ratio of the incidence of cases per 1000 person-years in the vaccinated group instead of the placebo group.
Scientists observed more frequent solicited local responses in the mRNA-1273 group, both after the first and second injections (94.2% and 93.4%, respectively), compared to the control group (36.8% and 32.6%, respectively). The main local reaction was injection site pain after the first and second injections. Systemic adverse reactions were also reported in the vaccinated group (68.5% of the participants after the first injection and 86.1% after the second injection). The most common of these were headaches, fatigue, chills, and myalgia.
These reactions lasted, on average, for about four days. The adverse reactions were roughly similar among participants aged 12 to 15 years and 16 to 17 years. No deaths or adverse events occurred. Further, no cases of myocarditis or pericarditis were reported. Fourteen days after the second injection, the vaccine's efficacy was challenging to estimate, mainly because of the low incidence of COVID-19 among adolescents. According to the less stringent CDC definition, the efficacy was 93.3% in the per-protocol population. The vaccine efficacy was 39.2% for asymptomatic infection after the second injection and 59.5%, 14 days after the first injection.
This study had some limitations. The efficacy analyses were secondary objectives because of milder COVID-19 disease among adolescents. There were also a relatively limited number of asymptomatic infections, which may have led to imprecise estimates of the confidence intervals. Finally, the trial population was less diverse than that in the phase 3 trial and less representative of the U.S. population.
Nevertheless, this study concluded that the mRNA-1273 vaccine is safe for adolescents as immune responses were similar to those of young adults (for whom the vaccine is approved), and the vaccine was effective in preventing COVID-19.
- Ali, K., et al. 2021. Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents. The New England Journal of Medicine. DOI: 10.1056/NEJMoa2109522