Article
作者: Koury, Kenneth ; Türeci, Özlem ; Patel, Sohil ; Arora, Samir ; Cannon, Kevin ; Lowry, Francine S ; Haggag, Amina ; Wadsworth, Larkin ; Fitz-Patrick, David ; Murray, Alexande ; Martin, Earl ; Chu, Laurence ; Raad, George ; Lee, Dung-Yang ; Rodriguez, Hecto ; Pickrell, Paul ; Rodriguez, Hector ; Senders, Shell ; Miller, Deon ; Usdan, Lisa ; Jennings, Timoth ; Mensa, Federico J ; Lu, Claire ; Şahin, Uğur ; Andrews, Charles ; Fortmann, Stephen ; Swanson, Kena A ; Christensen, Shane ; Wyper, Hayley ; Peterson, James ; Kitchin, Nicholas ; Gruber, William C ; Fragoso, Veronic ; Anderson, Annaliesa S ; Cooper, David ; Essink, Brando ; Davis, Matthe ; Chalhoub, Fadi ; Brandon, Donald ; Xu, Xia ; Lucasti, Christopher ; Finn, Daniel ; Hartman, Aaron ; Varano, Susann ; Stacey, Helen ; Heller, Robert
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