异源和同源mRNA-1273及BNT162b2疫苗接种的免疫原性和反应原性：一项多中心非劣效性随机试验。
Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial.
作者信息
Janssen Cécile, Cachanado Marine, Ninove Laetitia, Lachatre Marie, Michon Jocelyn, Epaulard Olivier, Maakaroun-Vermesse Zoha, Chidiac Christian, Laviolle Bruno, Aumaitre Hugues, Assaf Ady, Lacombe Karine, Schmidt-Mutter Catherine, Botelho-Nevers Elisabeth, Briere Magali, Boisson Thomas, Loubet Paul, Bienvenu Boris, Bouchaud Olivier, Touati Amel, Pereira Christine, Rousseau Alexandra, Berard Laurence, Montil Melissa, de Lamballerie Xavier, Simon Tabassome, Launay Odile
机构信息
Service de Maladies Infectieuses, Centre Hospitalier Annecy Genevois, Annecy 74370, France.
Inserm, F-CRIN, I REIVAC/COVIREIVAC, France.
出版信息
EClinicalMedicine. 2022 Jun;48:101444. doi: 10.1016/j.eclinm.2022.101444. Epub 2022 May 12.
BACKGROUND
Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination.
METHODS
We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467.
FINDINGS
Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 ( < 0·0001).
INTERPRETATION
The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic.
FUNDING
French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna.
背景
尽管针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的有效信使核糖核酸（mRNA）疫苗已在全球范围内推广使用，但其可互换性有助于扩大疫苗接种计划的规模。该试验的目的是评估异源SARS-CoV-2 mRNA初次疫苗接种诱导的免疫反应是否不劣于同源mRNA疫苗接种诱导的免疫反应。
方法
我们在18岁及以上接受第一剂SARS-CoV-2 mRNA疫苗的成年人中进行了一项多中心、随机、开放标签试验。参与者以1:1的比例随机分配，在第一剂疫苗接种后28至49天接受第二剂BNT162b2或mRNA-1273。随机分组根据首次接种的疫苗进行分层。主要终点是在第二剂疫苗接种后28天测量的抗刺突蛋白IgG抗体滴度。本研究已在ClinicalTrials.gov注册，试验编号为NCT04900467。
结果
在2021年5月28日至7月2日招募的414名随机参与者中，390名被纳入符合方案分析：第1组（BNT162b2/BNT162b2）94名参与者，第2组（BNT162b2/mRNA-1273）96名，第3组（mRNA-1273/mRNA-1273）97名，第4组（mRNA-1273/BNT162b2）103名。各异源方案相对于相应同源方案的抗刺突蛋白IgG抗体几何平均滴度比在第1组和第2组中为1.37（双侧95%置信区间，1.10至1.72），在第3组和第组中为0.67（双侧95%置信区间，0.55至0.82）。含有mRNA-1273的疫苗方案对主要流行的SARS-CoV-2病毒株的中和抗体水平更高。接受mRNA-1273作为第二剂的参与者比接受BNT162b2的参与者出现局部不良反应和全身症状的发生率更高（P<0.0001）。
解读
两种SARS-CoV-2 mRNA疫苗可灵活用于COVID-19初次疫苗接种的第二剂。尽管mRNA-1273的反应原性更强，但无论疫苗接种顺序如何，耐受性仍然良好。
资助
法国团结与卫生部和研究部。BNT162b2由辉瑞/生物新技术公司提供。mRNA-1273由莫德纳公司提供。
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