A Bivalent Omicron-BA.4/BA.5-Adapted BNT162b2 Booster in ≥12-Year-Olds

Clin Infect Dis. 2023 Nov 28:ciad718. doi: 10.1093/cid/ciad718. Online ahead of print.


Background: Protection against contemporary SARS-CoV-2 variants requires sequence-adapted vaccines.

Methods: In this ongoing phase 2/3 trial, 12-17-year-olds (n=108), 18-55-year-olds (n=313), and >55-year-olds (n=306) who previously received 3 original BNT162b2 30-µg doses, received a fourth dose (second booster) of 30-µg bivalent original/Omicron-BA.4/BA.5-adapted BNT162b2 (BNT162b2-Omi.BA.4/BA.5). For comparisons with original BNT162b2, participants were selected from another phase 3 trial. Immunologic superiority 1-month post-vaccination, with respect to 50% neutralizing titers (GMR lower bound [LB] 2-sided 95%CI >1), and noninferiority with respect to seroresponse rates (rate-difference LB 2-sided 95%CI >-5%), for Omicron BA.4/BA.5 were assessed in >55-year-olds versus original BNT162b2 as a second booster. Noninferiority with respect to neutralizing titer level (GMR LB 2-sided 95%CI >0.67) and seroresponse rate (rate-difference LB 2-sided 95%CI >-10%) of Omicron BA.4/BA.5 immune response for BNT162b2-Omi.BA.4/BA.5 in 18‒55-year-olds versus >55-year-olds was assessed.

Results: One-month post-vaccination in >55-year-olds, model-adjusted GMR of Omicron BA.4/BA.5 neutralizing titers for the BNT162b2-Omi.BA.4/BA.5 versus BNT162b2 group (2.91; 95%CI 2.45-3.44) demonstrated superiority of BNT162b2-Omi.BA.4/BA.5. Adjusted difference in percentages of >55-year-olds with seroresponse (26.77%; 95%CI 19.59-33.95) showed noninferiority of BNT162b2-Omi.BA.4/BA.5 to BNT162b2. Noninferiority of BNT162b2-Omi.BA.4/BA.5 in 18‒55-year-olds to >55-year-olds was met for model-adjusted GMR and seroresponse. GMTs in 12-17-year-olds increased from baseline to 1-month post-vaccination. The BNT162b2-Omi.BA.4/BA.5 safety profile was similar to booster doses of bivalent Omicron BA.1-modified BNT162b2 and original BNT162b2 reported in previous studies.

Conclusions: Based on immunogenicity and safety data up to 1-month post-vaccination in participants who previously received 3 original BNT162b2 doses, a BNT162b2-Omi.BA.4/BA.5 30 µg booster has a favorable benefit-risk profile.

Clinical trial registration: NCT05472038.

Keywords: BNT162b2 vaccine; Omicron variant; SARS-CoV-2; booster; children.

Associated data

  • ClinicalTrials.gov/NCT05472038