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Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age

Our take —

A two-dose regimen of the Pfizer vaccine (10 ug per dose, one third of the dose approved for individuals older than 11 years) was recently approved for emergency use in children aged 5-11 years in the United States. This study reported the results of related clinical trials that led to this emergency use authorization. In the initial dose-finding study, two 10-ug doses led to comparable neutralizing antibody levels with fewer adverse events than higher doses, and this was the dose carried forward into a larger randomized controlled trial of safety, immunogenicity, and efficacy. The two-dose regimen was 91% effective in preventing COVID-19, and provided a similar immune response to that observed in a cohort of 16-25 year olds who received the 30-ug dose approved for that age group. Adverse events associated with vaccination were generally mild and transient, with fever reported in 8% of vaccine recipients. There were no cases of myocarditis, though the study did not have enough participants to adequately assess the risks of this rare adverse event. Although the follow-up period was short (only about 2 months) and more data are forthcoming about longer-term safety and efficacy, these results provide strong justification for emergency use authorization of the vaccine among children aged 5-11 years.

Study design

Randomized Controlled Trial

Study population and setting

This publication reported the results from two related studies of the Pfizer COVID-19 vaccine among children aged 5-11 years: a Phase 1 dose-finding study and a Phase 2/3 randomized trial of safety, immunogenicity, and efficacy (ongoing, with results not yet available for children aged 6 months through 4 years). In the both studies, children with pre-existing conditions were eligible except those with immunocompromising conditions, those taking immunosuppressive therapy, or those with a history of MIS-C. For the Phase 1 study, entry criteria also included no prior COVID-19 diagnosis. The Phase 1 study (n=48, 50% male, mean age 7.9 years, 79% white) included 16 children assigned to each dosage arm (10 ug, 20 ug, and 30 ug), with blood samples collected at 7 days after the second dose for measurement of geometric mean SARS-CoV-2 neutralization titers (GMTs). In the Phase 2/3 study, 2,268 participants (52% male, mean age 8.2 years, 79% white) were assigned in a 2:1 ratio to two doses of either the vaccine (at a dose determined by Phase 1) or placebo. Immunogenicity was compared between a subset of study participants (n=485) and 350 16-25 year olds with respect to GMTs, increase in GMTs over one month, and the proportion of participants with seroresponse (defined by a 4-fold increase in titers from baseline). In this “immunobridging” analysis comparing the two age groups, success was defined by a point estimate of 0.8 or greater for the GMT ratio, with the lower limit of the 95% confidence interval greater than 0.67. For difference in seroresponse, immunobridging success was defined by the lower limit of the 95% confidence interval exceeding -10%. Efficacy was compared between those receiving the vaccine and placebo, starting 7 days after administration of the second dose, and was defined as 100 x (1-RR). Injections were administered in the Phase 1 study from March 24 to April 14, 2021. Randomization for the Phase 2/3 trial took place from June 7-19, 2021; median follow-up time was 2.3 months.

Summary of Main Findings

In the Phase 1 safety and immunogenicity dose-finding study, all local reactions were transient, with fever more common in the 30 ug group. There was one severe case of fever (39.7 degrees Celsius, resolving after one day) reported in a 10-year-old after the second dose of a 20 ug dose. The second dose was administered to the full group only for the 10 ug and 20 ug doses, and neutralizing GMTs 7 days after the second dose were 4163 for the 10 ug dose and 4583 for the 20 ug dose, and thus the 10 ug dose was selected for the Phase 2/3 trial. Among Phase 2/3 trial participants, adverse local reactions and systemic events were more common in the vaccine group (mostly mild to moderate, resolving in 1-2 days), with fatigue and headache as the most common systemic adverse events. Adverse events were more common after the second dose of vaccine, with fever occurring in 8.3% of vaccine recipients after either the first or second dose. One vaccine recipient experienced severe fever (40.0 degrees Celsius, resolving after one day). Severe adverse events were reported in 0.1% of vaccine recipients and 0.1% of placebo recipients; there were no deaths or adverse events leading to withdrawal. There were no reported cases of myocarditis or pericarditis. The geometric mean ratio of neutralizing GMTs (comparing 5-11 year olds receiving 10 ug to 16-25 year olds who received 30 ug) was 1.04 (95% CI: 0.93 to 1.18), which met the immunobridging criteria. The difference in percentage achieving seroresponse between age groups was 0.0% (-2.0% to 2.2%), which also met immunobridging criteria. Neutralizing GMTs 1 month after second dose were comparable between 5-11 year olds and 16-25 year olds (1198 vs. 1147), as were geometric mean fold rises from baseline to 1 month after second dose (118.2 vs. 111.4). Among participants with no prior evidence of SARS-CoV-2 infection, there were 3 cases of COVID-19 among vaccine recipients and 16 among placebo recipients (vaccine efficacy: 90.7%, 95% CI: 67.7% to 98.3%). There were no additional cases among participants with prior evidence of infection; the estimated vaccine efficacy among all participants was 90.7% (67.4% to 98.3%). There were no reported cases of severe COVID-19 or MIS-C.

Study Strengths

This was a randomized controlled trial. Immunogenicity was evaluated using a formal non-inferiority approach relative to serum neutralizing titers in an older age group. Detailed safety data on the vaccine was obtained and reported.


Although neutralizing antibody titers currently represent the best known correlate of immunity, there are likely other important determinants of immunity (e.g., T-cell response) that were not measured. The mean duration of follow-up was only 2.3 months, so it is not possible to infer vaccine effectiveness or adverse event incidence over longer durations; however, the study is ongoing. The study was not powered to assess risks of rare adverse events (e.g., myocarditis) that have been observed in other age groups, though an expanded cohort is currently being followed. The age range of 5 to 11 years represents a wide developmental spectrum; although the study was not designed to have adequate power for age-stratified analyses, it would have been informative if immunogenicity data had been presented by age strata. This study was conducted before widespread transmission of the delta variant. 

Value added

These results are the first from a randomized controlled trial of a COVID-19 vaccine among children aged 5-11 years.

This review was posted on: 8 December 2021