Evaluation of BNT162b2 Covid-19 Vaccine in Children Younger than 5 Years of Age

Abstract

Background: Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children.

Methods: We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2-3 safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present results for children 6 months to less than 2 years of age and those 2 to 4 years of age through the data-cutoff dates (April 29, 2022, for safety and immunogenicity and June 17, 2022, for efficacy). In the phase 2-3 trial, participants were randomly assigned (in a 2:1 ratio) to receive two 3-μg doses of BNT162b2 or placebo. On the basis of preliminary immunogenicity results, a third 3-μg dose (≥8 weeks after dose 2) was administered starting in January 2022, which coincided with the emergence of the B.1.1.529 (omicron) variant. Immune responses at 1 month after doses 2 and 3 in children 6 months to less than 2 years of age and those 2 to 4 years of age were immunologically bridged to responses after dose 2 in persons 16 to 25 years of age who received 30 μg of BNT162b2 in the pivotal trial.

Results: During the phase 1 dose-finding study, two doses of BNT162b2 were administered 21 days apart to 16 children 6 months to less than 2 years of age (3-μg dose) and 48 children 2 to 4 years of age (3-μg or 10-μg dose). The 3-μg dose level was selected for the phase 2-3 trial; 1178 children 6 months to less than 2 years of age and 1835 children 2 to 4 years of age received BNT162b2, and 598 and 915, respectively, received placebo. Immunobridging success criteria for the geometric mean ratio and seroresponse at 1 month after dose 3 were met in both age groups. BNT162b2 reactogenicity events were mostly mild to moderate, with no grade 4 events. Low, similar incidences of fever were reported after receipt of BNT162b2 (7% among children 6 months to <2 years of age and 5% among those 2 to 4 years of age) and placebo (6 to 7% among children 6 months to <2 years of age and 4 to 5% among those 2 to 4 years of age). The observed overall vaccine efficacy against symptomatic Covid-19 in children 6 months to 4 years of age was 73.2% (95% confidence interval, 43.8 to 87.6) from 7 days after dose 3 (on the basis of 34 cases).

Conclusions: A three-dose primary series of 3-μg BNT162b2 was safe, immunogenic, and efficacious in children 6 months to 4 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

Figure 1. Screening, Randomization, and Vaccine and Placebo Administration in the Phase 2–3 Trial.

At the data-cutoff date (April 29, 2022), the trial was ongoing, and the analyses included all the participants who had received the first dose by March 31, 2022. Therefore, some participants had not received dose 2, and many had not received dose 3 by the data-cutoff date. The phase 2–3 trial was conducted across 65 sites in Brazil, Finland, Poland, Spain, and the United States. Withdrawal by participant describes the inability of the participant to complete trial procedures or visits.

Figure 2. Local Reactions and Systemic Events Reported within 7 Days after Administration of BNT162b2 or Placebo in the Phase 2–3 Trial.

Results are for the blinded, placebo-controlled follow-up period. Shown are local reactions and systemic events after dose 1, dose 2, and dose 3 in BNT162b2 recipients (children 6 months to <2 years of age: dose 1, 1159 to 1173 participants; dose 2, 1137 to 1147 participants; and dose 3, 362 to 365 participants; and children 2 to 4 years of age: dose 1, 1813 to 1825 participants; dose 2, 1772 to 1779 participants; and dose 3, 547 to 552 participants) and in placebo recipients (children 6 months to <2 years of age: dose 1, 591 to 595 participants; dose 2, 590 or 591 participants; and dose 3, 170 participants; and children 2 to 4 years of age: dose 1, 905 to 909 participants; dose 2, 877 or 878 participants; and dose 3, 262 participants). Age-specific severity scales and descriptions for the two age groups are summarized in Table S4. Fever categories are designated in the key. 𝙸 bars represent 95% confidence intervals. The numbers above the bars show the percentage of participants in each group with at least one “yes” or “no” response for the specified event after the specified dose. Four participants 6 months to less than 2 years of age had a fever with a body temperature of more than 40.0°C (3 BNT162b2 recipients: day 1 after dose 1, day 1 after dose 2, and day 3 after dose 3 [1 participant each]; and 1 placebo recipient: day 5 after dose 1); 2 BNT162b2 recipients who had a fever with a body temperature of more than 40.0°C had a concurrent viral infection (roseola on the basis of clinical presentation or concurrent exanthem due to unspecified viral infection). Three BNT162b2 recipients 2 to 4 years of age had a fever with a body temperature of more than 40.0°C (day 2 after dose 1, day 4 after dose 2, and day 6 after dose 2 [1 participant each]), 1 of whom had a clinical presentation suggestive of viral exanthem such as roseola. Missing reactogenicity data were not imputed.

Figure 3. Vaccine Efficacy in Participants 6 Months to 4 Years of Age.

The data-cutoff date was June 17, 2022. Data are for participants without evidence of infection with severe acute respiratory syndrome coronavirus 2 before 7 days after dose 3 in the efficacy population that could be evaluated (defined in Table S1). Two-sided 95% confidence intervals for vaccine efficacy were derived with the use of the Clopper–Pearson method, with adjustment for surveillance time. The percentage of participants who reported symptoms but had missing results of polymerase-chain-reaction testing was small and not imputed in the analysis. Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point. The time period for accrual of coronavirus disease 2019 (Covid-19) cases is from 7 days after dose 3 to the end of the surveillance period. The inset shows the same data on an enlarged y axis.