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Randomized Controlled Trial
. 2021 Jul 15;385(3):239-250.
doi: 10.1056/NEJMoa2107456. Epub 2021 May 27.

Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents

Robert W Frenck Jr  1 , Nicola P Klein  1 , Nicholas Kitchin  1 , Alejandra Gurtman  1 , Judith Absalon  1 , Stephen Lockhart  1 , John L Perez  1 , Emmanuel B Walter  1 , Shelly Senders  1 , Ruth Bailey  1 , Kena A Swanson  1 , Hua Ma  1 , Xia Xu  1 , Kenneth Koury  1 , Warren V Kalina  1 , David Cooper  1 , Timothy Jennings  1 , Donald M Brandon  1 , Stephen J Thomas  1 , Özlem Türeci  1 , Dina B Tresnan  1 , Susan Mather  1 , Philip R Dormitzer  1 , Uğur Şahin  1 , Kathrin U Jansen  1 , William C Gruber  1 ; C4591001 Clinical Trial Group
Collaborators, Affiliations
Randomized Controlled Trial

Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents

Robert W Frenck Jr et al. N Engl J Med. .

Abstract

Background: Until very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of age. Safe, effective vaccines are needed to protect this population, facilitate in-person learning and socialization, and contribute to herd immunity.

Methods: In this ongoing multinational, placebo-controlled, observer-blinded trial, we randomly assigned participants in a 1:1 ratio to receive two injections, 21 days apart, of 30 μg of BNT162b2 or placebo. Noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants was an immunogenicity objective. Safety (reactogenicity and adverse events) and efficacy against confirmed coronavirus disease 2019 (Covid-19; onset, ≥7 days after dose 2) in the 12-to-15-year-old cohort were assessed.

Results: Overall, 2260 adolescents 12 to 15 years of age received injections; 1131 received BNT162b2, and 1129 received placebo. As has been found in other age groups, BNT162b2 had a favorable safety and side-effect profile, with mainly transient mild-to-moderate reactogenicity (predominantly injection-site pain [in 79 to 86% of participants], fatigue [in 60 to 66%], and headache [in 55 to 65%]); there were no vaccine-related serious adverse events and few overall severe adverse events. The geometric mean ratio of SARS-CoV-2 50% neutralizing titers after dose 2 in 12-to-15-year-old participants relative to 16-to-25-year-old participants was 1.76 (95% confidence interval [CI], 1.47 to 2.10), which met the noninferiority criterion of a lower boundary of the two-sided 95% confidence interval greater than 0.67 and indicated a greater response in the 12-to-15-year-old cohort. Among participants without evidence of previous SARS-CoV-2 infection, no Covid-19 cases with an onset of 7 or more days after dose 2 were noted among BNT162b2 recipients, and 16 cases occurred among placebo recipients. The observed vaccine efficacy was 100% (95% CI, 75.3 to 100).

Conclusions: The BNT162b2 vaccine in 12-to-15-year-old recipients had a favorable safety profile, produced a greater immune response than in young adults, and was highly effective against Covid-19. (Funded by BioNTech and Pfizer; C4591001 ClinicalTrials.gov number, NCT04368728.).

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Figures

Figure 1
Figure 1. Screening, Randomization, and Vaccine and Placebo Administration.
Participants who received dose 1 but not dose 2 could continue to be evaluated for safety. Participants were considered to have completed the vaccination period if they had completed the follow-up visit 1 month after dose 2 as of the data-cutoff date. As of the data-cutoff date, some participants had not yet completed their 1-month follow-up visit after dose 2. Some participants became eligible for a vaccine according to local or national recommendations before the 1-month follow-up visit after dose 2. These participants could choose to be made aware of their randomly assigned injection, and those who had received placebo could then choose to receive BNT162b2. Participants who had originally received placebo and chose to receive BNT162b2 as part of the trial would then follow a different visit schedule.
Figure 2
Figure 2. Local Reactions and Systemic Events Reported within 7 Days after Administration of BNT162b2 or Placebo.
The results shown are for the reactogenicity subset of the safety population, which included all participants in the 12-to-15-year-old cohort and the subset of participants in the 16-to-25-year-old cohort who had electronic diary data available. Pain at the injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity), or grade 4 (led to an emergency department visit or hospitalization). Redness and swelling were graded as mild (>2.0 to 5.0 cm in diameter), moderate (>5.0 to 10.0 cm in diameter), severe (>10.0 cm in diameter), or grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Fever categories are designated in the key. Fatigue, headache, chills, new or worsened muscle pain, and new or worsened joint pain were graded as mild (does not interfere with activity), moderate (some interference with activity), or severe (prevents daily routine activity). Vomiting was graded as mild (one or two times in 24 hours), moderate (more than two times in 24 hours), or severe (requires intravenous hydration), and diarrhea as mild (two or three loose stools in 24 hours), moderate (four or five loose stools in 24 hours), or severe (six or more loose stools in 24 hours). Grade 4 for all systemic events indicated an emergency department visit or hospitalization. 𝙸 bars indicate 95% confidence intervals. The numbers above the 𝙸 bars are the overall percentages of the participants in each group who reported the specified local reaction or systemic event. No participant had a grade 4 local reaction. With regard to systemic events, there was one incident of fever with a temperature higher than 40°C in a 12-to-15-year-old participant after dose 1 of BNT162b2.
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