TY - JOUR
T1 - Bivalent Omicron BA.1-Adapted BNT162b2 Booster in Adults Older than 55 Years
AU - Winokur, Patricia
AU - Gayed, Juleen
AU - Fitz-Patrick, David
AU - Thomas, Stephen J.
AU - Diya, Oyeniyi
AU - Lockhart, Stephen
AU - Xu, Xia
AU - Zhang, Ying
AU - Bangad, Vishva
AU - Schwartz, Howard I.
AU - Denham, Douglas
AU - Cardona, Jose F.
AU - Usdan, Lisa
AU - Ginis, John
AU - Mensa, Federico J.
AU - Zou, Jing
AU - Xie, Xuping
AU - Shi, Pei Yong
AU - Lu, Claire
AU - Buitrago, Sandra
AU - Scully, Ingrid L.
AU - Cooper, David
AU - Koury, Kenneth
AU - Jansen, Kathrin U.
AU - Türeci, Özlem
AU - Şahin, Uǧur
AU - Swanson, Kena A.
AU - Gruber, William C.
AU - Kitchin, Nicholas
N1 - Publisher Copyright:
© 2023 Massachusetts Medical Society.
PY - 2023/1/19
Y1 - 2023/1/19
N2 - Background: The emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. Methods: In an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-μg doses of the BNT162b2 vaccine were randomly assigned to receive 30 μg or 60 μg of BNT162b2, 30 μg or 60 μg of monovalent B.1.1.529 (omicron) BA.1-adapted BNT162b2 (monovalent BA.1), or 30 μg (15 μg of BNT162b2+15 μg of monovalent BA.1) or 60 μg (30 μg of BNT162b2+30 μg of monovalent BA.1) of BA.1-adapted BNT162b2 (bivalent BA.1). Primary objectives were to determine superiority (with respect to 50% neutralizing titer [NT50] against BA.1) and noninferiority (with respect to seroresponse) of the BA.1-adapted vaccines to BNT162b2 (30 μg). A secondary objective was to determine noninferiority of bivalent BA.1 to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain. Exploratory analyses assessed immune responses against omicron BA.4, BA.5, and BA.2.75 subvariants. Results: A total of 1846 participants underwent randomization. At 1 month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) showed neutralizing activity against BA.1 superior to that of BNT162b2 (30 μg), with NT50 geometric mean ratios (GMRs) of 1.56 (95% confidence interval [CI], 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively. Bivalent BA.1 (both doses) and monovalent BA.1 (60 μg) were also noninferior to BNT162b2 (30 μg) with respect to seroresponse against BA.1; between-group differences ranged from 10.9 to 29.1 percentage points. Bivalent BA.1 (either dose) was noninferior to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain, with NT50 GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. BA.4-BA.5 and BA.2.75 neutralizing titers were numerically higher with 30-μg bivalent BA.1 than with 30-μg BNT162b2. The safety profile of either dose of monovalent or bivalent BA.1 was similar to that of BNT162b2 (30 μg). Adverse events were more common in the 30-μg monovalent-BA.1 (8.5%) and 60-μg bivalent-BA.1 (10.4%) groups than in the other groups (3.6 to 6.6%). Conclusions: The candidate monovalent or bivalent omicron BA.1-adapted vaccines had a safety profile similar to that of BNT162b2 (30 μg), induced substantial neutralizing responses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutralized BA.4, BA.5, and BA.2.75 strains.
AB - Background: The emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. Methods: In an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-μg doses of the BNT162b2 vaccine were randomly assigned to receive 30 μg or 60 μg of BNT162b2, 30 μg or 60 μg of monovalent B.1.1.529 (omicron) BA.1-adapted BNT162b2 (monovalent BA.1), or 30 μg (15 μg of BNT162b2+15 μg of monovalent BA.1) or 60 μg (30 μg of BNT162b2+30 μg of monovalent BA.1) of BA.1-adapted BNT162b2 (bivalent BA.1). Primary objectives were to determine superiority (with respect to 50% neutralizing titer [NT50] against BA.1) and noninferiority (with respect to seroresponse) of the BA.1-adapted vaccines to BNT162b2 (30 μg). A secondary objective was to determine noninferiority of bivalent BA.1 to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain. Exploratory analyses assessed immune responses against omicron BA.4, BA.5, and BA.2.75 subvariants. Results: A total of 1846 participants underwent randomization. At 1 month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) showed neutralizing activity against BA.1 superior to that of BNT162b2 (30 μg), with NT50 geometric mean ratios (GMRs) of 1.56 (95% confidence interval [CI], 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively. Bivalent BA.1 (both doses) and monovalent BA.1 (60 μg) were also noninferior to BNT162b2 (30 μg) with respect to seroresponse against BA.1; between-group differences ranged from 10.9 to 29.1 percentage points. Bivalent BA.1 (either dose) was noninferior to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain, with NT50 GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. BA.4-BA.5 and BA.2.75 neutralizing titers were numerically higher with 30-μg bivalent BA.1 than with 30-μg BNT162b2. The safety profile of either dose of monovalent or bivalent BA.1 was similar to that of BNT162b2 (30 μg). Adverse events were more common in the 30-μg monovalent-BA.1 (8.5%) and 60-μg bivalent-BA.1 (10.4%) groups than in the other groups (3.6 to 6.6%). Conclusions: The candidate monovalent or bivalent omicron BA.1-adapted vaccines had a safety profile similar to that of BNT162b2 (30 μg), induced substantial neutralizing responses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutralized BA.4, BA.5, and BA.2.75 strains.
KW - Coronavirus
KW - Infectious Disease
KW - Vaccines
KW - Viral Infections
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U2 - 10.1056/NEJMoa2213082
DO - 10.1056/NEJMoa2213082
M3 - Article
C2 - 36652353
AN - SCOPUS:85146532110
SN - 0028-4793
VL - 388
SP - 214
EP - 227
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 3
ER -