Pfizer Inc. and BioNTech SE announced positive results from a Phase 2/3 clinical trial evaluating the safety, tolerability, and immunogenicity of a 10-µg booster (third) dose of the Pfizer-BioNTech COVID-19 vaccine in healthy children 5 through 11 years of age, according to a news release.
These data demonstrate an increase in SARS-CoV-2 Omicron variant and wild-type strain neutralizing titers following a booster dose of the Pfizer-BioNTech COVID-19 vaccine compared to two doses. These data reinforce the potential function of a third dose of the vaccine in maintaining high levels of protection against the virus in this age group.
In the Phase 2/3 clinical trial, data were analyzed from 140 children 5 through 11 years of age received a booster dose approximately 6 months after the second dose of the Pfizer-BioNTech COVID-19 vaccine 10-µg primary series. Data from a sub analysis of 30 sera from this study indicate that serum antibodies induced by a third dose neutralize the SARS-CoV-2 Omicron variant in this age group, as demonstrated by a 36-fold increase in neutralizing antibody titers compared to levels seen after two doses of the Pfizer-BioNTech COVID-19 Vaccine. A robust response was observed regardless of prior SARS-CoV-2 infection.
Further, immunogenicity data from 140 participants in the Phase 2/3 clinical trial with who had no evidence of prior SARS-CoV-2 infection showed a 6-fold increase (95% CI: 5.0, 7.6) in SARS-CoV-2 wild-type strain–neutralizing geometric mean titers (GMTs) one month after the booster compared to the SARS-CoV-2–neutralizing GMTs one month after the second dose of the Pfizer-BioNTech COVID-19 vaccine, demonstrating a strong immune response in this age group. To date, more than 10,000 children under the age of 12 have participated in clinical trials investigating the Pfizer-BioNTech COVID-19 vaccine, and in this most recent booster data readout (n=401), the vaccine was well tolerated with no new safety signals observed.
Pfizer and BioNTech plan to submit a request for Emergency Use Authorization (EUA) of a booster dose for children ages 5 through 11 in the U.S. in the coming days. The companies also plan to share these data with the European Medicines Agency (EMA) and other regulatory agencies around the world as soon as possible.
A primary series of two 10-µg doses of the Pfizer-BioNTech COVID-19 Vaccine was previously authorized under EUA for this age group in October 2021. The 10-µg dose level was carefully selected based on safety, tolerability, and immunogenicity data.
The Phase 1/2/3 trial initially enrolled up to 4,500 children ages 6 months to under 12 years of age in the United States, Finland, Poland, and Spain from more than 90 clinical trial sites. Additional children have been enrolled in all age groups following study amendments and the trial currently includes more than 10,000 children. The trial was originally designed to evaluate the safety, tolerability, and immunogenicity of the Pfizer BioNTech vaccine on a two-dose schedule (approximately 21 days apart) in three age groups: ages 5 to under 12 years; ages 2 to under 5 years; and ages 6 months to under 2 years. Based on the Phase 1 dose-escalation portion of the trial, children ages 5 to under 12 years received a two-dose schedule of 10 µg each while children under age 5 received a lower 3 µg dose for each injection in the Phase 2/3 study. The trial enrolled children with or without prior evidence of SARS-CoV-2 infection. In December 2021, Pfizer and BioNTech announced the companies would test a third 3 µg dose given at least two months after the second dose in children under age 5 and a third dose of the 10 µg formulation in children 5 to under 12 years of age.
To evaluate the effectiveness of a third 10-µg dose in children 5 through 11 years of age, Pfizer and BioNTech tested a panel of 30 human immune sera obtained from the blood of individuals that received two or three 10-µg doses of the current Pfizer-BioNTech COVID-19 Vaccine, using a live SARS-CoV-2 recombinant virus fluorescent foci reduction neutralization test (FFRNT). Each serum was tested simultaneously for its neutralizing titer against recombinant SARS-CoV-2 (with USA-WA-1/2020 genetic backbone) bearing the wild-type SARS-CoV-2 spike protein and the Omicron spike. The 50% neutralizing geometric mean titer (GMT) against Omicron was 993 (after three doses), compared to 27 after two doses. The neutralizing GMT against the wild-type virus was 2153 (after three doses), compared to 335 after two doses. Further analysis will assess the persistence of neutralizing titers over time after a booster dose of the Pfizer-BioNTech COVID-19 Vaccine against the Omicron and wild-type strains.