柳叶刀: 同时接种新冠肺炎疫苗和季节性流感疫苗不会引起安全问题

背景:


同时接种新冠肺炎和流感疫苗可以减轻卫生保健系统的负担。研究者的目标是评估同时使用ChAdOx1BNT162b2和适龄流感疫苗的安全性。


方法:


在这项多中心、随机、对照、第4阶段试验中,接受单剂ChAdox1BNT162b2的成年人在英国12个地点登记,并被随机分配(1:1)在接种第二剂新冠肺炎疫苗的同时,同时接种与年龄相适应的流感疫苗或安慰剂。3周后,接受安慰剂的那组人接种了流感疫苗,反之亦然。对参与者进行了6周的随访。流感疫苗是三种季节性灭活疫苗(三价、MF59C佐剂或细胞或重组四价疫苗)。参与者和调查人员被蒙住了分配的面具。主要终点是一个或多个参与者报告的在第一次试验疫苗接种后7天内引起的全身反应,差异不到25%被认为是非劣质的。分析是在意向治疗的基础上进行的。还评估了局部和主动的全身反应和体液反应。该试验在ISRCTN注册,ISRCTN14391248


结果:


202141日至626日期间,679名参与者被招募到以下六个队列之一:129ChAdOx1+细胞四价流感疫苗,139BNT162b2+细胞四价流感疫苗,146ChAdOx1+MF59C佐剂,三价流感疫苗,79BNT162b2+MF59C佐剂,三价流感疫苗,128ChAdOx1+重组四价流感疫苗,以及58BNT162b2+重组四价流感疫苗。340名参与者被分配到同时接种流感疫苗和第二剂新冠肺炎疫苗,在第0天接种第二剂新冠肺炎疫苗,随后在第21天接种安慰剂。339名参与者被随机分配到同时接种安慰剂和第二剂新冠肺炎疫苗,在第0天接种流感疫苗,然后在第21天接种流感疫苗。在四个队列中显示出非劣势:ChAdOx1+细胞四价流感疫苗(流感疫苗减去安慰剂-1·29%,95%CI-14.712.1),BNT162b2+细胞四价流感疫苗(6.17%,-6.2718.6),BNT162b2+MF59C佐剂三价流感疫苗(-12.9%,-34.2%8.37。在其他两个队列中,95%CI上限超过0.25非劣势界限(ChAdOx1+MF59C佐剂,三价流感疫苗10.3%,-5.44~26.0;BNT162b2+重组四价流感疫苗6.75%,-11.8~25.3)。大多数接种疫苗的全身反应是轻度或中度的。在随机分配的两组中,局部和主动全身反应的发生率相似。一个严重的不良事件,严重头痛的住院,被认为与试验干预有关。免疫反应没有受到不利影响。


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参与者在第二次接种COVID疫苗加接种流感疫苗或安慰剂完整病例分析后的7天内报告了一种或多种要求的系统性不良反应

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接种或不接种流感疫苗的新冠肺炎疫苗之间的抗尖峰免疫球蛋白几何平均滴度比


结论:


同时接种ChAdOx1BNT162b2加上适合年龄的流感疫苗不会引起安全问题,并保留了对这两种疫苗的抗体反应。在下一个免疫季节同时接种新冠肺炎和流感疫苗应会减轻提供疫苗的卫生保健服务的负担,使有需要的人能够及时接种疫苗并免受新冠肺炎和流感的影响。


原文摘要:



Background


Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine.


Methods


In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine. 3 weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed up for 6 weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted or a cellular or recombinant quadrivalent vaccine).  Participants and investigators were masked to the allocation.  The primary endpoint was one or more participant-reported solicited systemic reactions in the 7 days after first trial vaccination(s), with a difference of less than 25% considered non-inferior. Analyses were done on an intention-to-treat basis. Local and unsolicited systemic reactions and humoral responses were also assessed. The trial is registered with ISRCTN, ISRCTN14391248.


Findings


Between April 1 and June 26, 2021, 679 participants were recruited to one of six cohorts, as follows: 129 ChAdOx1 plus cellular quadrivalent influenza vaccine, 139 BNT162b2 plus cellular quadrivalent influenza vaccine, 146 ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine, 79 BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine, 128 ChAdOx1 plus recombinant quadrivalent influenza vaccine, and 58 BNT162b2 plus recombinant quadrivalent influenza vaccine. 340 participants were assigned to concomitant administration of influenza and a second dose of COVID-19 vaccine at day 0 followed by placebo at day 21, and 339 participants were randomly assigned to concomitant administration of placebo and a second dose of COVID-19 vaccine at day 0 followed by influenza vaccine at day 21. Non-inferiority was indicated in four cohorts, as follows: ChAdOx1 plus cellular quadrivalent influenza vaccine (risk difference for influenza vaccine minus placebo –1·29%, 95% CI –14·7 to 12·1), BNT162b2 plus cellular quadrivalent influenza vaccine (6·17%, –6·27 to 18·6), BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine (–12·9%, –34·2 to 8·37), and ChAdOx1 plus recombinant quadrivalent influenza vaccine (2·53%,

–13·3 to 18·3). In the other two cohorts, the upper limit of the 95% CI exceeded the 0·25 non-inferiority margin (ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine 10·3%, –5·44 to 26·0; BNT162b2 plus recombinant quadrivalent influenza vaccine 6·75%, –11·8 to 25·3). Most systemic reactions to vaccination were mild or moderate. Rates of local and unsolicited systemic reactions were similar between the randomly assigned groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention.  Immune responses were not adversely affected.


Interpretation


Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need.


参考文献:


Rajeka Lazarus, et al., (2021). Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial. The Lancet, DOI: https://doi.org/10.1016/S0140-6736(21)02329-1






           


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