Bethune C

Boffito M

Bula M

Burns F

Chalkias S

Chen X

Clark R

Cosgrove CA

Dargan PI

Darton TC

Das R

Deng W

deWindt E

Duncan CJA

Dutko FJ

Feng J

Galiza EP

Girard B

Heath PT

Kalra PA

Lee IT

Lillie PJ

Mehta S

Miller JM

Moore P

Moran E

Nally R

Parker C

Rust D

SanFrancisco-Ramos A

Saralaya D

Sheridan R

Study Investigators

Sutherland A

Tomassini JE

Tracy L

Zhou H

Background: The omicron BA.1 bivalent booster is used globally. Previous open-label studies of the omicron BA.1 (Moderna mRNA-1273.214) booster showed superior neutralising antibody responses against omicron BA.1 and other variants compared with the original mRNA-1273 booster. We aimed to compare the safety and immunogenicity of omicron BA.1 monovalent and bivalent boosters with the original mRNA-1273 vaccine in a large, randomised controlled trial. Methods: In this large, randomised, observer-blind, active-controlled, phase 3 trial in the UK (28 hospital and vaccination clinic sites), individuals aged 16 years or older who had previously received two injections of any authorised or approved COVID-19 vaccine, with or without an mRNA vaccine booster (third dose), were randomly allocated (1:1) using interactive response technology to receive 50 μg omicron BA.1 monovalent or bivalent vaccines or 50 μg mRNA-1273 administered as boosters via deltoid intramuscular injection. The primary outcomes were safety and immunogenicity at day 29, including prespecified non-inferiority and superiority of booster immune responses, based on the neutralising antibody geometric mean concentration (GMC) ratios of the monovalent and bivalent boosters compared with mRNA-1273. Safety was assessed in all participants who received first or second boosters, and primary immunogenicity outcomes were assessed in all participants who received the planned booster dose, had pre-booster and day 29 antibody data, had no major protocol deviations, and who were SARS-CoV-2-negative. The study is registered with EudraCT (2022-000063-51) and ClinicalTrials.gov (NCT05249829) and is ongoing. Findings: Between Feb 16 and March 24, 2022, 724 participants were randomly allocated to receive omicron BA.1 monovalent (n=366) or mRNA-1273 (n=357), and between April 2 and June 17, 2022, 2824 participants were randomly allocated to receive omicron BA.1 bivalent (n=1418) or mRNA-1273 (n=1395) vaccines as second boosters. Median durations (months) between the most recent COVID-19 vaccine and study boosters were similar for omicron BA.1 monovalent (4\ub70 months [IQR 3\ub76-4\ub77]) and mRNA-1273 (4\ub71 [3\ub75-4\ub77]), and for the omicron BA.1 bivalent (5\ub75 [4\ub78-6\ub72]) and mRNA-1273 (5\ub74 [4\ub78-6\ub72]) boosters. The omicron BA.1 monovalent and bivalent boosters elicited superior neutralising GMCs against the omicron BA.1 variant compared with mRNA-1273, with GMC ratios of 1\ub768 (99% CI 1\ub745-1\ub795) and 1\ub753 (1\ub741-1\ub767) at day 29 post-booster doses in participants without previous SARS-CoV-2 infection. Both boosters induced non-inferior ancestral SARS-CoV-2 (Asp614Gly) immune responses with GMCs that were similar for the bivalent (2987\ub72 [95% CI 2814\ub79-3169\ub79]) versus mRNA-1273 (2911\ub73 [2750\ub79-3081\ub70]) and lower for the monovalent (2699\ub77 [2431\ub73-2997\ub77] vs 3020\ub76 [2776\ub75-3286\ub72]) boosters, with respective GMC ratios of 1\ub705 (99% CI 0\ub796-1\ub715) and 0\ub782 (95% CI 0\ub774-0\ub791). Results were comparable regardless of previous SARS-CoV-2 infection status. Incidences of solicited adverse reactions with the omicron BA.1 monovalent (335 [91\ub73%] of 367 participants) and omicron BA.1 bivalent (1285 [90\ub74%] of 1421 participants) boosters were similar to those observed previously for mRNA-1273, with no new safety concerns identified and no occurrences of fatal adverse events

Newcastle University E-Prints

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Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial

Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial

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