Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents

Abstract

Background: The incidence of coronavirus disease 2019 (Covid-19) among adolescents between 12 and 17 years of age was approximately 900 per 100,000 population from April 1 through June 11, 2021. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in adolescents are unknown.

Methods: In this ongoing phase 2-3, placebo-controlled trial, we randomly assigned healthy adolescents (12 to 17 years of age) in a 2:1 ratio to receive two injections of the mRNA-1273 vaccine (100 μg in each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of mRNA-1273 in adolescents and the noninferiority of the immune response in adolescents as compared with that in young adults (18 to 25 years of age) in a phase 3 trial. Secondary objectives included the efficacy of mRNA-1273 in preventing Covid-19 or asymptomatic severe acute respiratory syndrome coronavirus 2 infection.

Results: A total of 3732 participants were randomly assigned to receive mRNA-1273 (2489 participants) or placebo (1243 participants). In the mRNA-1273 group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 93.1% and 92.4%, respectively), headache (in 44.6% and 70.2%, respectively), and fatigue (in 47.9% and 67.8%, respectively); in the placebo group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 34.8% or 30.3%, respectively), headache (in 38.5% and 30.2%, respectively), and fatigue (in 36.6% and 28.9%, respectively). No serious adverse events related to mRNA-1273 or placebo were noted. The geometric mean titer ratio of pseudovirus neutralizing antibody titers in adolescents relative to young adults was 1.08 (95% confidence interval [CI], 0.94 to 1.24), and the absolute difference in serologic response was 0.2 percentage points (95% CI, -1.8 to 2.4), which met the noninferiority criterion. No cases of Covid-19 with an onset of 14 days after the second injection were reported in the mRNA-1273 group, and four cases occurred in the placebo group.

Conclusions: The mRNA-1273 vaccine had an acceptable safety profile in adolescents. The immune response was similar to that in young adults, and the vaccine was efficacious in preventing Covid-19. (Funded by Moderna and the Biomedical Advanced Research and Development Authority; Teen COVE ClinicalTrials.gov number, NCT04649151.).

Figure 1. Randomization and Analysis Populations.

The full analysis population consisted of all participants who had undergone randomization and received at least one injection of mRNA-1273 or placebo; the per-protocol population consisted of all participants in the full analysis population who had received planned injections of mRNA-1273 or placebo, complied with the timing of the second injection, had no immunologic and virologic evidence of previous Covid-19 at baseline, and had no major protocol deviations; the modified intention-to-treat (mITT) population consisted of all participants in the full analysis population who had no serologic or virologic evidence of previous SARS-CoV-2 infection before the first injection (both a negative reverse-transcriptase–polymerase-chain-reaction [RT-PCR] test for SARS-CoV-2 and a negative serologic test based on binding antibodies specific to SARS-CoV-2 nucleocapsid) at baseline; the mITT1 population consisted of all participants in the mITT population with the exclusion of those who received the incorrect injection; and the safety population consisted of all participants who received at least one injection. The per-protocol immunogenicity subpopulation consisted of randomly selected participants who had received the planned injections of mRNA-1273 or placebo according to schedule, complied with the timing of the second injection, had no immunologic and virologic evidence of previous Covid-19 at baseline, complied with the immunogenicity testing schedule, and had no major protocol deviations that affected the key or critical data; participants who were seropositive at baseline were excluded from the per-protocol immunogenicity subpopulation. Two participants who received placebo did not receive the second injection and then discontinued the trial later for a reason listed as “other.” One participant who received mRNA-1273 did not receive the second injection and continued in the trial.

Figure 2. Solicited Local and Systemic Adverse Reactions.

Shown is the percentage of participants who had a solicited local or systemic adverse reaction within 7 days after the first or second injection (dose 1 or dose 2) of either mRNA-1273 vaccine or placebo.

Figure 3. Secondary Analyses of Efficacy.

Vaccine efficacy was calculated as 1 minus the ratio of the incidence of SARS-CoV-2 infection per 1000 person-years (mRNA-1273 vs. placebo). The primary definition of Covid-19 was at least two systemic symptoms or at least one respiratory symptom plus at least one nasopharyngeal swab, nasal swab, or saliva sample that was positive for SARS-CoV-2 by RT-PCR. The secondary case definition of Covid-19 was at least one systemic or respiratory symptom plus a swab that was positive for SARS-CoV-2 by RT-PCR. The category of SARS-CoV-2 infection (regardless of symptoms) was defined as a combination of postbaseline symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in participants with a negative SARS-CoV-2 status at baseline. Asymptomatic SARS-CoV-2 infection was defined as the absence of symptoms and infections detected by a postbaseline positive RT-PCR or serologic test in participants with a negative SARS-CoV-2 status at baseline. The per-protocol (PP) population consisted of all participants who had received at least one injection of mRNA-1273 or placebo and received planned injections of mRNA-1273 or placebo, complied with the timing of the second injection, had no immunologic and virologic evidence of previous Covid-19 at baseline, and had no major protocol deviations; this population included 1042 participants in the placebo group and 2139 participants in the mRNA-1273 group. The modified intention-to-treat population with the exclusion of those who had received the incorrect injection (mITT1) consisted of all participants who had no serologic or virologic evidence of previous SARS-CoV-2 infection before the first injection of mRNA-1273 or placebo (both a negative RT-PCR test for SARS-CoV-2 and a negative serologic test based on binding antibodies specific to SARS-CoV-2 nucleocapsid at baseline; this population included 1073 participants in the placebo group and 2163 participants in the mRNA-1273 group. NE denotes not estimated.