Immunogenicity and Safety of a Third COVID-19 BNT162b2 mRNA Vaccine Dose in 5- to 11-Year Olds

Abstract

In this ongoing study, substantially increased ancestral SARS-CoV-2 neutralizing responses were observed 1 month after a third 10-µg BNT162b2 dose given to 5 to 11-year olds versus neutralizing responses post-dose 2. After dose 3, increased neutralizing responses against Omicron BA.1 and BA.4/BA.5 strains were also observed. The safety/tolerability profile was acceptable. (NCT04816643).

Keywords: BNT162b2 vaccine; COVID-19; booster; children; immunogenicity; safety.

Figure 1.

Serum SARS-CoV-2 neutralization titers 1 month after BNT162b2 doses 2 and 3 in participants without evidence of prior SARS-CoV-2 infection. In Panel A, 50% neutralizing titers were determined in a validated microneutralization assay against ancestral SARS-CoV-2 strain (USA-WA1/2020). Results are in the dose 2 and dose 3 evaluable immunogenicity populations (defined in Supplementary Figure 1). The n value for the before dose 1 timepoint is the total number of participants who were either dose 2 evaluable or dose 3 evaluable. Values within the bars are GMTs (95% CIs). The geometric mean ratio (GMR) shown is 1 month after dose 3 to 1 month after dose 2 and the geometric mean fold rise (GMFR) shown is from before dose 3 to 1 month after dose 3. Assay results below the lower limit of quantitation (LLOQ) of 41 were set to 0.5 × LLOQ. In Panel B, 50% serum neutralizing titers against ancestral SARS-CoV-2 and the Omicron BA.1 and BA.4/BA.5 sublineages are shown. Values within the bars are GMTs (95% CIs) and the GMR after dose 3 to after dose 2 are shown above the bars. Assay results below the LLOQ of 20 were set to 0.5 × LLOQ. Results are in the Omicron neutralization subset (defined in Supplementary Figure 1A) and based on the Fluorescent Focus Reduction Neutralization Test (FFRNT). Results in participants with and without prior SARS-CoV-2 infection are in Supplementary Figure 2.

Figure 2.

Local reactions and systemic events. Panel A shows local reactions and Panel B shows systemic events in BNT162b2 recipients with electronic-diary data after dose 1 (n = 398), dose 2 (n = 399), and dose 3 (n = 371). Grading of reactogenicity events is outlined in the Appendix. Numbers above the bars are the percentage of participants with that local reaction or systemic event with any severity within 7 days after each dose. One participant experienced fever of >40.0 °C after dose 2 (body temperature of 39.7 °C on day 2 and 40.3 °C on day 3). This participant also had a fever of 39.0 °C occurring 1 day after dose 3, which resolved within 3 days with the use of concomitant medication. Technical issues that impacted activation of the electronic diary after dose 3 resulted in 36 participants not recording events on day 1 after dose 3. For 11 of these participants, events were recorded by day 2. For the remaining 25 participants, study site staff contacted participants/parents/legal guardians regarding the occurrence of reactogenicity events; only 1 participant had fatigue and injection site pain.