1. BNT162b2 mRNA Covid-19 vaccine was efficacious in preventing symptomatic Covid-19 in children 5 to 11 years of age.
2. The BNT162b2 vaccine had a favorable safety profile with no serious adverse events reported.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The BNT162B2 vaccine, containing lipid nanoparticles carrying mRNA which encodes the SARS-CoV-2 viral spike glycoprotein, has received authorization for adults and older children. With rising case numbers among school-age children, an appreciable risk of severe illness and complications, and the emergence of highly transmissible variants, the need for safe and effective Covid-19 vaccines remains high in this age group. This article reported results from a phase 1 dose-identifying study and an ongoing phase 2-3 safety and efficacy trial, investigating the BNT162b2 vaccine given to healthy children 5 to 11 years old. During the open-label phase 1, 3 groups received 2 vaccine doses 21 days apart at 10-, 20-, or 30-µg per dose, respectively. Based on safety and immunogenicity findings, 10-µg was selected for the randomized placebo-controlled phase 2-3. During this phase, it was found that BNT162b2 yielded non-inferior immunogenicity to the 16-to-25-year-olds, provided 90.7% efficacy against SARS-CoV-2 infection, and was not associated with severe adverse effects. While the follow-up period was limited, long-term monitoring will continue and these results provided robust support for vaccinating 5-to-11-year-old children with two 10-µg doses of BNT162b2.
In-Depth [randomized controlled trial]: This study reported results from an open-label dose level-identifying Phase 1 trial and a double-blind randomized placebo-controlled Phase 2-3 trial. These trials investigated the administration of the BNT162b2 mRNA vaccine against Covid-19 in participants 6 months to 11 years of age. The results reported were from the 5-to-11-year-old subgroup. 2 doses of BNT162b2 were administered 21 days apart. Children were included if they had no or stable pre-existing conditions. Children were excluded if they had an immunocompromising condition, were on immunosuppressive therapies, or had a history of a multisystem inflammatory syndrome in children (MIS-C). In phase 1, children were also excluded if they had previous clinical or virologic Covid-19 diagnoses. In phase 1, 48 children 5 to 11 years old received the vaccine at 10, 20, or 30 µg per dose (16 per dose level). In phase 2-3, 2268 children were randomly assigned at 2:1 ratio to receive the BNT162b2 vaccine (10 µg dose) (1517 children) or placebo (751 children). Safety was assessed via reactogenic events, as well as serious adverse events, including myocarditis. Immunogenicity was measured from blood samples via SARS-CoV-2 neutralization titers, and noninferiority was determined relative to titers obtained from the 16-to-25-year-old participants. Efficacy was evaluated against confirmed Covid-19 with onset at least 7 days after the second dose. During phase 1, higher dose levels (20- or 30-µg) were associated with more fever and severe adverse events while the 10-µg dose yielded comparable immunogenicity to higher dose levels. Hence, 10 µg was selected for Phase 2-3. During phase 2-3, local reaction and systemic events, such as fatigue, headache, chills, and muscle pains, were more common in BNT162b2 than placebo, especially following the second dose. Fever and antipyretics use was also more common following the second dose than the first. No serious adverse events were reported to be linked to the vaccine or placebo. No deaths, myocarditis, pericarditis, or anaphylaxis were reported. Regarding immunogenicity, the geometric mean ratio of SARS-CoV-2 neutralizing titers from 10 µg of BNT162b2 in 5-to-11-year-olds versus that from 30 µg in 16-to-25-year-olds 1 month after the second dose was 1.04 (95% confidence interval [CI], 0.93 to 1.18), meeting the pre-specified immunobridging non-inferiority criterion. Among children without evidence of previous SARS-CoV-2 infection, 3 Covid-19 cases were reported among BNT162b2 recipients while 16 were reported in the placebo group, resulting in the efficacy of 90.7% (95% CI, 67.7 to 98.3). No additional cases were reported in children with evidence of the previous infection. No severe Covid-19 or MIS-C was reported. While this study only reported the short-term results (median follow-up of 2.3 months), longer-term monitoring of safety and efficacy is underway. These results support a vaccination schedule consisting of two 10-µg doses of BNT162b2 for children 5 to 11 years of age against Covid-19.
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