A Bivalent Omicron-BA.4/BA.5-Adapted BNT162b2 Booster in ≥12-Year-Olds
Author:
Usdan Lisa1, Patel Sohil2, Rodriguez Hector3, Xu Xia4, Lee Dung-Yang4, Finn Daniel5, Wyper Hayley2, Lowry Francine S4, Mensa Federico J6, Lu Claire7, Cooper David7, Koury Kenneth7, Anderson Annaliesa S7, Türeci Özlem6, Şahin Uğur6, Swanson Kena A7, Gruber William C7, Kitchin Nicholas2, Andrews Charles, Arora Samir, Brandon Donald, Cannon Kevin, Chalhoub Fadi, Christensen Shane, Chu Laurence, Davis Matthe, Essink Brando, Finn Daniel, Fitz-Patrick David, Fortmann Stephen, Fragoso Veronic, Haggag Amina, Hartman Aaron, Heller Robert, Jennings Timoth, Lucasti Christopher, Martin Earl, Miller Deon, Murray Alexande, Peterson James, Pickrell Paul, Raad George, Rodriguez Hecto, Senders Shell, Stacey Helen, Usdan Lisa, Varano Susann, Wadsworth Larkin,
Affiliation:
1. CNS Healthcare , Memphis, Tennessee , USA 2. Vaccine Research and Development, Pfizer , Hurley , United Kingdom 3. Acevedo Clinical Research Associates , Miami, Florida , USA 4. Vaccine Research and Development, Pfizer , Collegeville, Pennsylvania , USA 5. Kentucky Pediatric/Adult Research , Bardstown, Kentucky , USA 6. BioNTech , Mainz , Germany 7. Vaccine Research and Development, Pfizer , Pearl River, New York , USA
Abstract
Abstract
Background
Protection against contemporary severe acute respiratory syndrome coronavirus 2 (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 after vaccination, with respect to 50% neutralizing titers (lower bound [LB] of 2-sided 95% confidence interval [CI] for geometric mean ratio [GMR], >1), and noninferiority with respect to seroresponse rates (LB of 2-sided 95% CI for rate difference, greater than −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 (LB of 2-sided 95% CI for GMR, > 0.67) and seroresponse rate (LB of 2-sided 95% CI for rate difference, greater than −10%) of Omicron BA.4/BA.5 immune response for BNT162b2-Omi.BA.4/BA.5 in 18–55 versus >55-year-olds was assessed.
Results
One month after vaccination in >55-year-olds, the model-adjusted GMR of Omicron BA.4/BA.5 neutralizing titers for the BNT162b2-Omi.BA.4/BA.5 versus BNT162b2 groups (2.91 [95% CI, 2.45–3.44]) demonstrated the superiority of BNT162b2-Omi.BA.4/BA.5. Adjusted difference in the 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 compared with >55-year-olds was met for model-adjusted GMR and seroresponse. Geometric mean titers in 12–17-year-olds increased from baseline to 1 month after vaccination. The BNT162b2-Omi.BA.4/BA.5 safety profile was similar to the profiles for 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 after 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 Trials Registration
NCT05472038
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
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