Background: The BNT162b2 vaccine is safe and effective for COVID-19 prevention. BNT162b2 safety and immunogenicity have been evaluated in immunocompromised individuals in real-world observational studies, particularly in pediatric populations, but not in clinical trials. Methods: This phase 2b single-arm trial descriptively evaluated a Dose 3 (age-appropriate) BNT162b2 primary series with a Dose 4 in immunocompromised individuals 2-<5, 5-<12, 12-<18, and ≥18 years of age without a previous clinical or microbiological COVID-19 diagnosis. Primary objectives were to describe immune responses, reactogenicity, and adverse events following vaccination. Results: Out of 124 participants enrolled, 119 received Dose 3 and 90 received Dose 4. Among participants without evidence of past SARS-CoV-2 infection, neutralizing geometric mean titers (GMTs) and geometric mean fold rises (GMFRs) against the SARS-CoV-2 ancestral strain ranged from 344.6 to 1584.4 and 7.9 to 36.4 at 1 month after Dose 3 and from 1474.0 to 4157.9 and 31.0 to 95.6 at 1 month after Dose 4, respectively, across age groups. Among participants with or without evidence of past infection, GMTs and GMFRs ranged from 787.1 to 2940.6 and 9.6 to 54.3 at 1 month after Dose 3 and from 1031.3 to 13,457.1 and 9.1 to 220.0 at 1 month after Dose 4. Percentages of participants with or without evidence of past SARS-CoV-2 infection achieving seroresponse ranged from 50.0 to 92.9% at 1 month after Dose 3, and from 75.0 to 100% and 33.3 to 100.0% at 1 and 6 months after Dose 4 across age groups, respectively. No new safety signals were identified. Conclusions: BNT162b2 was immunogenic, increasing GMTs in immunocompromised individuals ≥2 years old, particularly after Doses 3 and 4. GMT increases were generally similar across age groups and disease subsets. Three or four BNT162b2 doses had a favorable risk-benefit profile in this population.
