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Safety and Immunogenicity of a Fourth Dose of Omicron-BA.1-Adapted BNT162b2 COVID-19 Vaccines in Adults 18‒55 Years Old
Journal article   Open access   Peer reviewed

Safety and Immunogenicity of a Fourth Dose of Omicron-BA.1-Adapted BNT162b2 COVID-19 Vaccines in Adults 18‒55 Years Old

Patricia Winokur, Oyeniyi Diya, David Fitz-Patrick, Michael Dever, Juleen Gayed, Stephen Lockhart, Xia Xu, Ying Zhang, Vishva Bangad, L Tyler Wadsworth, …
Clinical infectious diseases
01/21/2026
DOI: 10.1093/cid/ciag026
PMID: 41560517
url
https://doi.org/10.1093/cid/ciag026View
Published (Version of record) Open Access

Abstract

Emergence of SARS-CoV-2 sublineages warrants the use of sequence-adapted vaccines to provide protection against COVID-19. In this phase 3 trial, adults 18‒55 years old who had previously received three 30-μg doses of BNT162b2 vaccine were randomized to receive a 60- or 30-μg dose of bivalent Omicron BA.1‒adapted BNT162b2 comprising equal amounts of ancestral and monovalent messenger RNA BA.1 (bivalent BA.1) or a 60-μg dose of monovalent Omicron BA.1‒adapted BNT162b2 (monovalent BA.1). Safety (local reactions, systemic events, adverse events [AEs], and serious AEs) was the primary objective. Exploratory analyses assessed immune responses against Omicron-BA.1, BA.4, and BA.5 subvariants and ancestral strain. Among the 1054 randomized participants who received monovalent BA.1 or bivalent BA.1, frequencies of local reactions, systemic events, and AEs were slightly higher with 60-µg monovalent BA.1 than either bivalent BA.1 dose level. One month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) induced substantial neutralizing responses against Omicron BA.1 (50% neutralizing titer geometric mean fold rises [GMFRs]: 15.4 [95% CI 12.4-19.2], 17.1 [13.7-21.4], and 24.6 [19.3-31.4], respectively) and ancestral strain (GMFRs: 6.2 [5.1-7.6], 7.3 [6.0-8.9], and 7.0 [5.7-8.7], respectively). In a smaller (n=30/treatment arm) sentinel cohort, all study vaccines modestly neutralized Omicron BA.4 and BA.5. Bivalent and monovalent BA.1‒adapted vaccines had a safety profile similar to original BNT162b2 30 μg and induced substantial neutralizing responses against Omicron BA.1 and ancestral strains.NCT04955626.
COVID-19 SARS-CoV-2 vaccine BNT162b2 Omicron variants BA.1

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