新英格兰|辉瑞新冠疫苗在青少年上的临床试验最新成果&心肌炎临床诊断的重大突破

 

背景


截止到2021年5月21日,新冠病毒Covid-19已经导致全球1.65亿人感染,34万人死亡,因此亟需开发安全有效的疫苗以达到群体免疫。BNT162b2是辉瑞研发的一款mRNA疫苗,其编码SARS-CoV-2刺突糖蛋白。在健康成年人中,BNT162b2能够产生高效的中和滴度及强烈的CD4+与CD8+抗原特异性反应,在16周岁以上1-2-3期临床实验中具有很好的安全性,第二针剂注射7天后有效率可以达到95%,因此在2020年12月11日,BNT162b2获得了FDA的紧急使用授权应用于16周岁以上成年人,并且基于此项研究,在2021年5月10日,获得了全球唯一授权应用于12周岁以上成年人。孩子和青少年相对于成年人Covid-19症状较轻,但是随着成年人普遍注射疫苗,年轻人将构成Covid-19感染的主要群体,目前疫情已经严重影响青少年的教育及社交活动,同时,加重了监护人的负担,因此对于青少年研发安全有效的疫苗具有重要意义。


2021年5月11日,Robert W. Frenck等研究者在《新英格兰医学杂志》上发表了一项多国家的、安慰剂对照的、单盲的临床研究结果,评估了新冠疫苗BNT162b2对于青少年的安全性、免疫原性及有效性。


方法


按照1:1的比例将受试者分为两组,注射 2针剂30 μg BNT162b2 或安慰剂,中间间隔21天。与 16 至 25 岁参与者相比,12 至 15 岁参与者对 BNT162b2 的免疫反应的非劣效性是一个免疫原性目标。在12至15岁确诊Covid-19队列中评估安全性(反应原性及不良事件)及有效性。


结果


共有2260 名 12 至 15 岁的青少年接受了注射,1131 人接受 BNT162b2,1129 人接受安慰剂。正如在其他年龄组中发现的那样,BNT162b2 具有良好的安全性和副作用特征。主要是短暂的轻度至中度反应原性(主要是注射部位疼痛 [79% 至 86% 的参与者],疲劳 [60% 至 66% ] 和头痛 [55% 至 65%]);没有疫苗相关的严重不良事件,总体严重不良事件很少。与 16 至 25 岁参与者相比,12 至 15 岁参与者注射2针剂后SARS-CoV-2 50% 中和滴度的几何平均比为 1.76(95% 置信区间 [CI] , 1.47 至 2.10)。符合两侧 95% 置信区间下限大于 0.67 的非劣效性标准,表明 12 至 15 岁队列的免疫反应更大。在没有 SARS-CoV-2 感染的参与者中,在 BNT162b2 接受者中没有发现在第 2 剂后 7 天或更长时间发病的 Covid-19 病例,在安慰剂接受者中发生了 16 例,观察到的疫苗有效性为 100%(95% CI,75.3 至 100)。

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SARS-CoV-2血清中和实验


结论


BNT162b2疫苗在12至15岁的受试者中具有良好的安全性,比年轻成年人产生更大的免疫反应,并且对Covid-19高度有效。


原文摘要:


BACKGROUND


Until very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of age. Safe, effective vaccines are needed to protect this population, facilitate in-person learning and socialization, and contribute to herd immunity.


METHODS


In this ongoing multinational, placebo-controlled, observer-blinded trial, we randomly assigned participants in a 1:1 ratio to receive two injections, 21 days apart, of 30 μg of BNT162b2 or placebo. Noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-yearold participants was an immunogenicity objective. Safety (reactogenicity and adverse events) and efficacy against confirmed coronavirus disease 2019 (Covid-19; onset, ≥7 days after dose 2) in the 12-to-15-year-old cohort were assessed.


RESULTS


Overall, 2260 adolescents 12 to 15 years of age received injections; 1131 received BNT162b2, and 1129 received placebo. As has been found in other age groups, BNT162b2 had a favorable safety and side-effect profile, with mainly transient mild to-moderate reactogenicity (predominantly injection-site pain [in 79 to 86% of participants], fatigue [in 60 to 66%], and headache [in 55 to 65%]); there were no vaccine related serious adverse events and few overall severe adverse events. The geometric mean ratio of SARS-CoV-2 50% neutralizing titers after dose 2 in 12-to-15-year-old participants relative to 16-to-25-year-old participants was 1.76 (95% confidence interval [CI], 1.47 to 2.10), which met the noninferiority criterion of a lower boundary of the two-sided 95% confidence interval greater than 0.67 and indicated a greater response in the 12-to-15-year-old cohort. Among participants without evidence of previous SARS-CoV-2 infection, no Covid-19 cases with an onset of 7 or more days after dose 2 were noted among BNT162b2 recipients, and 16 cases occurred among placebo recipients. The observed vaccine efficacy was 100% (95% CI, 75.3 to 100).


CONCLUSIONS


The BNT162b2 vaccine in 12-to-15-year-old recipients had a favorable safety profile, produced a greater immune response than in young adults, and was highly effective against Covid-19. (Funded by BioNTech and Pfizer; C4591001 ClinicalTrials.gov number, NCT04368728.)


参考文献:


Robert W. Frenck, Jr., M.D., Nicola P. Klein, et al. Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. N Engl J Med. DOI: 10.1056/NEJMoa2107456





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