Moderna, Cambridge, MA, USA.
Vaccine Institute, Centre for Neonatal and Paediatric Infection, St George's University of London, London, UK.
Lancet Infect Dis. 2023 Sep;23(9):1007-1019. doi: 10.1016/S1473-3099(23)00295-5. Epub 2023 Jun 19.
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.
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.
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 SARS-CoV-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.
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.
Moderna.
奥密克戎 BA.1 二价疫苗在全球范围内使用。先前关于奥密克戎 BA.1（Moderna mRNA-1273.214）加强针的开放标签研究表明，与原始的 mRNA-1273 加强针相比，针对奥密克戎 BA.1 和其他变体的中和抗体反应具有优越性。我们旨在比较奥密克戎 BA.1 单价和二价加强针与原始 mRNA-1273 疫苗在一项大型随机对照试验中的安全性和免疫原性。
在英国的这项大型、随机、观察者盲法、主动对照、3 期试验（28 个医院和疫苗接种诊所地点）中，先前接受过任何授权或批准的 COVID-19 疫苗两剂接种的 16 岁或以上个体，无论是否接种了 mRNA 疫苗加强针（第三剂），使用交互式反应技术随机分配（1:1）接受 50 μg 奥密克戎 BA.1 单价或二价疫苗或 50 μg mRNA-1273 作为加强针，通过三角肌肌内注射。主要结局是第 29 天的安全性和免疫原性，包括基于单价和二价加强针与 mRNA-1273 的中和抗体几何平均浓度（GMC）比值的预设非劣效性和优越性。在接受第一或第二加强针的所有参与者中评估安全性，在接受计划加强针剂量、有预加强针和第 29 天抗体数据、无主要方案偏差且 SARS-CoV-2 阴性的所有参与者中评估主要免疫原性结局。该研究在 EudraCT（2022-000063-51）和 ClinicalTrials.gov（NCT05249829）上注册，正在进行中。
在 2022 年 2 月 16 日至 3 月 24 日期间，724 名参与者被随机分配接受奥密克戎 BA.1 单价（n=366）或 mRNA-1273（n=357），在 2022 年 4 月 2 日至 6 月 17 日期间，2824 名参与者被随机分配接受奥密克戎 BA.1 二价（n=1418）或 mRNA-1273（n=1395）疫苗作为第二加强针。奥密克戎 BA.1 单价（4.0 个月[IQR 3.6-4.7]）和 mRNA-1273（4.1[3.5-4.7]）之间以及奥密克戎 BA.1 二价（5.5 个月[4.8-6.2]）和 mRNA-1273（5.4[4.8-6.2]）之间最近一次 COVID-19 疫苗和研究加强针之间的中位持续时间（月）相似。在没有先前 SARS-CoV-2 感染的参与者中，奥密克戎 BA.1 单价和二价加强针针对奥密克戎 BA.1 变体诱导出了优越的中和 GMC，其在第 29 天的 GMC 比值分别为 1.68（99%CI 1.45-1.95）和 1.53（1.41-1.67）。两种加强针均诱导出对原始 SARS-CoV-2（Asp614Gly）免疫反应的非劣效性，二价疫苗的 GMC 与 mRNA-1273 相似（2987.2[95%CI 2814.9-3169.9]），而单价疫苗的 GMC 较低（2699.7[2431.3-2997.7]比 3020.6[2776.5-3286.2]），相应的 GMC 比值分别为 1.05（99%CI 0.96-1.15）和 0.82（95%CI 0.74-0.91）。无论先前是否感染 SARS-CoV-2，结果都是可比的。奥密克戎 BA.1 单价（367 名参与者中的 335 名[91.3%]）和奥密克戎 BA.1 二价（1421 名参与者中的 1285 名[90.4%]）加强针的不良事件发生率与先前观察到的 mRNA-1273 相似，没有发现新的安全性问题，也没有发生致命的不良事件。
含有奥密克戎的疫苗加强针针对奥密克戎 BA.1 产生了优越的免疫原性，并对原始株产生了相当的免疫原性，没有新的安全性问题。随着不同的 SARS-CoV-2 变体不断出现，持续监测免疫反应和真实世界的疫苗有效性仍然很重要。
Moderna。
