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Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years

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 th...

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Autores principales: Winokur, Patricia, Gayed, Juleen, Fitz-Patrick, David, Thomas, Stephen J., Diya, Oyeniyi, Lockhart, Stephen, Xu, Xia, Zhang, Ying, Bangad, Vishva, Schwartz, Howard I., Denham, Douglas, Cardona, Jose F., Usdan, Lisa, Ginis, John, Mensa, Federico J., Zou, Jing, Xie, Xuping, Shi, Pei-Yong, Lu, Claire, Buitrago, Sandra, Scully, Ingrid L., Cooper, David, Koury, Kenneth, Jansen, Kathrin U., Türeci, Özlem, Şahin, Uğur, Swanson, Kena A., Gruber, William C., Kitchin, Nicholas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Massachusetts Medical Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933930/
https://www.ncbi.nlm.nih.gov/pubmed/36652353
http://dx.doi.org/10.1056/NEJMoa2213082
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author Winokur, Patricia
Gayed, Juleen
Fitz-Patrick, David
Thomas, Stephen J.
Diya, Oyeniyi
Lockhart, Stephen
Xu, Xia
Zhang, Ying
Bangad, Vishva
Schwartz, Howard I.
Denham, Douglas
Cardona, Jose F.
Usdan, Lisa
Ginis, John
Mensa, Federico J.
Zou, Jing
Xie, Xuping
Shi, Pei-Yong
Lu, Claire
Buitrago, Sandra
Scully, Ingrid L.
Cooper, David
Koury, Kenneth
Jansen, Kathrin U.
Türeci, Özlem
Şahin, Uğur
Swanson, Kena A.
Gruber, William C.
Kitchin, Nicholas
author_facet Winokur, Patricia
Gayed, Juleen
Fitz-Patrick, David
Thomas, Stephen J.
Diya, Oyeniyi
Lockhart, Stephen
Xu, Xia
Zhang, Ying
Bangad, Vishva
Schwartz, Howard I.
Denham, Douglas
Cardona, Jose F.
Usdan, Lisa
Ginis, John
Mensa, Federico J.
Zou, Jing
Xie, Xuping
Shi, Pei-Yong
Lu, Claire
Buitrago, Sandra
Scully, Ingrid L.
Cooper, David
Koury, Kenneth
Jansen, Kathrin U.
Türeci, Özlem
Şahin, Uğur
Swanson, Kena A.
Gruber, William C.
Kitchin, Nicholas
author_sort Winokur, Patricia
collection PubMed
description 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 [NT(50)] 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 NT(50) 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 NT(50) 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. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04955626.)
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spelling pubmed-99339302023-02-22 Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years Winokur, Patricia Gayed, Juleen Fitz-Patrick, David Thomas, Stephen J. Diya, Oyeniyi Lockhart, Stephen Xu, Xia Zhang, Ying Bangad, Vishva Schwartz, Howard I. Denham, Douglas Cardona, Jose F. Usdan, Lisa Ginis, John Mensa, Federico J. Zou, Jing Xie, Xuping Shi, Pei-Yong Lu, Claire Buitrago, Sandra Scully, Ingrid L. Cooper, David Koury, Kenneth Jansen, Kathrin U. Türeci, Özlem Şahin, Uğur Swanson, Kena A. Gruber, William C. Kitchin, Nicholas N Engl J Med Original Article 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 [NT(50)] 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 NT(50) 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 NT(50) 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. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04955626.) Massachusetts Medical Society 2023-01-19 /pmc/articles/PMC9933930/ /pubmed/36652353 http://dx.doi.org/10.1056/NEJMoa2213082 Text en Copyright © 2023 Massachusetts Medical Society. All rights reserved. http://www.nejmgroup.org/legal/terms-of-use.htm This article is made available via the PMC Open Access Subset for unrestricted re-use, except commercial resale, and analyses in any form or by any means with acknowledgment of the original source. PMC is granted a license to make this article available via PMC and Europe PMC, subject to existing copyright protections.
spellingShingle Original Article
Winokur, Patricia
Gayed, Juleen
Fitz-Patrick, David
Thomas, Stephen J.
Diya, Oyeniyi
Lockhart, Stephen
Xu, Xia
Zhang, Ying
Bangad, Vishva
Schwartz, Howard I.
Denham, Douglas
Cardona, Jose F.
Usdan, Lisa
Ginis, John
Mensa, Federico J.
Zou, Jing
Xie, Xuping
Shi, Pei-Yong
Lu, Claire
Buitrago, Sandra
Scully, Ingrid L.
Cooper, David
Koury, Kenneth
Jansen, Kathrin U.
Türeci, Özlem
Şahin, Uğur
Swanson, Kena A.
Gruber, William C.
Kitchin, Nicholas
Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years
title Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years
title_full Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years
title_fullStr Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years
title_full_unstemmed Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years
title_short Bivalent Omicron BA.1–Adapted BNT162b2 Booster in Adults Older than 55 Years
title_sort bivalent omicron ba.1–adapted bnt162b2 booster in adults older than 55 years
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933930/
https://www.ncbi.nlm.nih.gov/pubmed/36652353
http://dx.doi.org/10.1056/NEJMoa2213082
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