13th November 2021, Dr Chee L Khoo
The TGA is examining data from Pfizer on the BNT162b2 vaccination in children between 5-11 years old as I write this article. The US FDA have already approved the vaccine for use in children of those age groups and the US CDC has recommended that children 5-11 years receive the vaccine. So, it is expected that our TGA will approve the vaccine in a similar manner but whether it is recommended for children is up to the ATAGI people. Many parents are already asking questions about the vaccine. We better be informed about the safety and efficacy of the vaccines in this age group. Should my child have the vaccine?
Because older children and adults have now achieved high vaccination rates, school-age children now account for an increasing proportion of cases and hospitalisations. We now hear about frequent school outbreaks occurring resulting in interrupted education and adversely affected children’s social and emotional development and mental health. Preventing SARS-CoV-2 infection in children will protect against severe disease, hospitalisations as well as severe or long-term complications including multisystem inflammatory syndrome in children (MIS-C).
In addition, reducing infections in this age bracket may reduced transmission in the home, at school and in the wider community. Children could also potentially become ongoing reservoirs of infection and sources of newly emerging variants.
In an ongoing phase 2–3 randomised trial is being conducted to investigate the safety, immunogenicity and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age (1). During the earlier phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study in Phase 2/3.
Phase 2/3 Results
Compared with the larger adult trials, the trial in children 5-11 years was small. 2268 children were randomly assigned to receive two doses of BNT162b2 vaccine (1517 children) or saline placebo (751 children) three weeks apart. The median follow-up was 2.3 months.
We know from efficacy trials in children 16-25 years that two doses of BNT162b2 vaccines are immunogenic (2,3). In this trial, blood samples were collected for immunogenicity assessments, which included determination of SARS-CoV-2 neutralisation titres. They compared the neutralisation titres in 5-11 years with those in 16-25 years. The geometric mean ratio of neutralising titres (GMTs) for 10 μg of BNT162b2 in 5-to-11-year-olds to that for 30 μg of BNT162b2 in 16-to-25-year-olds 1 month after the second dose was 1.04. This means the robust virus-neutralising response observed in 5-to-11-year-olds was similar to that seen in 16-to-25-year-olds from the pivotal trial, which demonstrated 95% vaccine efficacy among persons at least 16 years of age from 7 days to
approximately 2 months after the second dose (3).
Among participants without evidence of previous SARS-CoV-2 infection, there were three cases
of Covid-19 (with onset 7 days or more after the second dose) among BNT162b2 recipients and
16 among placebo recipients; the observed vaccine efficacy was 90.7%.
BNT162b2 recipients reported more local reactions and systemic events than placebo recipients. The reactions and events reported were generally mild to moderate, lasting 1 to 2 days. Injection-site pain was the most common local reaction, occurring in 71 to 74% of BNT162b2 recipients. Severe injection-site pain after the first or second dose was reported in 0.6% of BNT162b2 recipients and in no placebo recipients.
Fatigue and headache were the most frequently reported systemic events (0.9%), headache (0.3%), chills (0.1%), and muscle pain (0.1%) were also reported after the first or second dose of BNT162b2. Frequencies of fatigue, headache, and chills were similar among BNT162b2 and placebo recipients after the first dose and were more frequent among BNT162b2 recipients than among placebo recipients after the second dose.
In general, systemic events were reported more often after the second dose of BNT162b2 than after the first dose. Fever occurred in 8.3% of BNT162b2 recipients after the first or second dose.
Compared with adults and adolescents in the pivotal trial, 5-to-11-year-olds reported a higher
incidence of injection-site redness (15 to 19%, vs. 5 to 7%) and swelling (10 to 15%, vs. 5 to 8%), but a generally lower incidence of systemic events, including fever (3 to 7%, vs. 1 to 20%) and chills (5 to 10%, vs. 6 to 42%) (2,3). Lymphadenopathy was reported in 0.9% of 5-to-11-year-old BNT162b2 recipients, an incidence similar to that in 12-to-15-year-olds (0.8%) but higher than that observed in adults (0.3%) (2,3). No MIS-C cases were reported, although surveillance continues. Neither myocarditis nor pericarditis was observed, a finding consistent with the low frequency of these adverse events with real-world use of BNT162b2 in other age groups (4).
In summary, two 10-μg doses of the BNT162b2 vaccine administered 21 days apart were safe, immunogenic, and 90.7% effective against Covid-19 in 5-to-11-year-old children.
- Walter EB, Talaat KR, Sabharwal C, et al. Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age. N Engl J Med. 2021 Nov 9. doi: 10.1056/NEJMoa2116298. Epub ahead of print. PMID: 34752019.
- Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; 383: 2603-15.
- Frenck RW Jr, Klein NP, Kitchin N, et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med 2021; 385: 239-50.
- Cai C, Peng Y, Shen E, et al. A comprehensive analysis of the efficacy and safety of COVID-19 vaccines. Mol Ther 2021; 29:2794-805.