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

被引：37

作者：

Lee, Ivan ^{[1
,22
]}

Cosgrove, Catherine A. ^{[2
]}

Moore, Patrick ^{[3
,4
]}

Bethune, Claire ^{[5
]}

Nally, Rhiannon ^{[6
]}

Bula, Marcin ^{[7
]}

Kalra, Philip A. ^{[8
]}

Clark, Rebecca ^{[9
]}

Dargan, Paul, I ^{[10
]}

Boffito, Marta ^{[11
,12
]}

Sheridan, Ray ^{[13
]}

Moran, Ed ^{[14
]}

Darton, Thomas C. ^{[15
]}

Burns, Fiona ^{[16
]}

Saralaya, Dinesh ^{[17
,18
]}

Duncan, Christopher J. A. ^{[19
,20
]}

Lillie, Patrick J. ^{[21
]}

Ramos, Alberto San Francisco ^{[2
]}

Galiza, Eva P. ^{[2
]}

Heath, Paul ^{[2
]}

Girard, Bethany ^{[1
]}

Parker, Christy ^{[1
]}

Rust, Dondi ^{[1
]}

Mehta, Shraddha ^{[1
]}

de Windt, Elizabeth ^{[1
]}

Sutherland, Andrea ^{[1
]}

Tomassini, Joanne E. ^{[1
]}

Dutko, Frank J. ^{[1
]}

Chalkias, Spyros ^{[1
]}

Deng, Weiping ^{[1
]}

Chen, Xing ^{[1
]}

Feng, Jing ^{[1
]}

Tracy, Laree ^{[1
]}

Zhou, Honghong ^{[1
]}

Miller, Jacqueline M. ^{[1
]}

Das, Rituparna ^{[1
]}

机构：

[1] Moderna, Cambridge, MA USA

[2] St Georges Univ London, Inst Infect & Immun, Ctr Neonatal & Paediat Infect & Vaccine Inst, London, England

[3] Adam Practice, Poole, Dorset, England

[4] Univ Hosp Southampton NHS Fdn Trust, Palliat Med, Southampton, Hampshire, England

[5] Univ Hosp Plymouth NHS Trust, Plymouth, Devon, England

[6] Wansford & Kings Cliffe Practice, Wansford, England

[7] Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3BX, Merseyside, England

[8] Northern Care Alliance NHS Fdn Trust, Salford Royal Hosp, Salford, England

[9] Lancashire Cardiac Ctr, Blackpool, England

[10] Guys & St ThomasNHS Fdn Trust London, London, England

[11] Chelsea & Westminster Hosp NHS Fdn Trust, London, England

[12] Imperial Coll London, Dept Infect Dis, London, England

[13] Royal Devon & Exeter Hosp, Exeter, Devon, England

[14] Southmead Hosp, Bristol, Avon, England

[15] Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, England

[16] Royal Free London NHS Fdn Trust, Univ Coll London, London NW3 2QG, England

[17] Educ & Hlth Comm, Bradford, W Yorkshire, England

[18] Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England

[19] Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne, Northumberland, England

[20] Newcastle Tyne Hosp NHS Fdn Trust, NIHR Newcastle Clin Res Facil, Newcastle Upon Tyne, England

[21] Hull Univ Teaching Hosp NHS Trust, Castle Hill Hosp, Cottingham, England

[22] Moderna, Cambridge, MA 02139 USA

来源：

LANCET INFECTIOUS DISEASES | 2023年 / 23卷 / 09期

关键词：

D O I：

10.1016/S1473-3099(23)00295-5

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

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 mu g omicron BA.1 monovalent or bivalent vaccines or 50 mu g 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-2negative. 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 (4.0 months [IQR 3.6-4.7]) and mRNA-1273 (4.1 [3.5-4.7]), and for the omicron BA.1 bivalent (5.5 [4.8-6.2]) and mRNA-1273 (5.4 [4.8-6.2]) 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 1.68 (99% CI 1.45-1.95) and 1.53 (1.41-1.67) 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 (2987.2 [95% CI 2814.9-3169.9]) versus mRNA-1273 (2911.3 [2750.9-3081.0]) and lower for the monovalent (2699.7 [2431.3-2997.7] vs 3020.6 [2776.5-3286.2]) boosters, with respective GMC ratios of 1.05 (99% CI 0.96-1.15) and 0.82 (95% CI 0.74-0.91). Results were comparable regardless of previous SARSCoV-2 infection status. Incidences of solicited adverse reactions with the omicron BA.1 monovalent (335 [91.3%] of 367 participants) and omicron BA.1 bivalent (1285 [90.4%] 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. Interpretation Omicron-containing booster vaccines generated superior immunogenicity against omicron BA.1 and comparable immunogenicity against the original strain with no new safety concerns. It remains important to continuously monitor the immune responses and real-world vaccine effectiveness as divergent SARS-CoV-2 variants emerge. Copyright (c) 2023 Elsevier Ltd. All rights reserved.

引用

页码：1007 / 1019

页数：13

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