评价 BNT162b2 新冠疫苗在 5 岁以下儿童中的效果。
Evaluation of BNT162b2 Covid-19 Vaccine in Children Younger than 5 Years of Age.
机构信息
From Texas Children's Hospital, Baylor College of Medicine, Houston (F.M.M.), and the University of Texas Medical Branch, Galveston (J.Z., X. Xie, P.-Y.S.); Peninsula Research Associates, Rolling Hills Estates (L.D.S.), and Stanford University School of Medicine, Palo Alto (Y.M.) - both in California; Vaccine Research and Development, Pfizer, Pearl River (C.S., A.G., U.N.S., C.H., M.I., B.A.P., I.M., K.A.S., K.K., C.L., D.C., K.U.J., W.C.G.), and SUNY Upstate Medical University, Syracuse (J.B.D.) - both in New York; Vaccine Research and Development (X. Xu, H.M.), and Worldwide Safety, Safety Surveillance and Risk Management (S.M.), Pfizer, Collegeville, PA; Vaccine Research and Development, Pfizer, Hurley, United Kingdom (N.K., S.L., C.W., L.C.); Atlanta Center for Medical Research, Atlanta (R.R.); Spring Valley Pediatrics, Washington, DC (J.M.S.); Katedra Pediatrii, Instytut Nauk Medycznych, Kolegium Nauk Medycznych, Uniwersytet Rzeszowski, Rzeszow, Poland (H.C.); the Department of Pediatrics, University of Cincinnati College of Medicine, and the Division of Pediatric Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati (G.C.P.); Duke Human Vaccine Institute, Durham, NC (E.B.W.); Johns Hopkins University, Baltimore (K.R.T.); Seattle Children's Hospital, Seattle (J.A.E.); Tampere University, Espoo Vaccine Research Clinic, Espoo, Finland (B.U.); Hospital Universitario HM Puerta del Sur, Madrid (S.N.M.); and BioNTech, Mainz, Germany (Ö.T., U.Ş.).
出版信息
N Engl J Med. 2023 Feb 16;388(7):621-634. doi: 10.1056/NEJMoa2211031.
BACKGROUND
Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children.
METHODS
We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2-3 safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present results for children 6 months to less than 2 years of age and those 2 to 4 years of age through the data-cutoff dates (April 29, 2022, for safety and immunogenicity and June 17, 2022, for efficacy). In the phase 2-3 trial, participants were randomly assigned (in a 2:1 ratio) to receive two 3-μg doses of BNT162b2 or placebo. On the basis of preliminary immunogenicity results, a third 3-μg dose (≥8 weeks after dose 2) was administered starting in January 2022, which coincided with the emergence of the B.1.1.529 (omicron) variant. Immune responses at 1 month after doses 2 and 3 in children 6 months to less than 2 years of age and those 2 to 4 years of age were immunologically bridged to responses after dose 2 in persons 16 to 25 years of age who received 30 μg of BNT162b2 in the pivotal trial.
RESULTS
During the phase 1 dose-finding study, two doses of BNT162b2 were administered 21 days apart to 16 children 6 months to less than 2 years of age (3-μg dose) and 48 children 2 to 4 years of age (3-μg or 10-μg dose). The 3-μg dose level was selected for the phase 2-3 trial; 1178 children 6 months to less than 2 years of age and 1835 children 2 to 4 years of age received BNT162b2, and 598 and 915, respectively, received placebo. Immunobridging success criteria for the geometric mean ratio and seroresponse at 1 month after dose 3 were met in both age groups. BNT162b2 reactogenicity events were mostly mild to moderate, with no grade 4 events. Low, similar incidences of fever were reported after receipt of BNT162b2 (7% among children 6 months to <2 years of age and 5% among those 2 to 4 years of age) and placebo (6 to 7% among children 6 months to <2 years of age and 4 to 5% among those 2 to 4 years of age). The observed overall vaccine efficacy against symptomatic Covid-19 in children 6 months to 4 years of age was 73.2% (95% confidence interval, 43.8 to 87.6) from 7 days after dose 3 (on the basis of 34 cases).
CONCLUSIONS
A three-dose primary series of 3-μg BNT162b2 was safe, immunogenic, and efficacious in children 6 months to 4 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).
背景
在年幼儿童中，急需安全有效的针对 2019 年冠状病毒病（Covid-19）的疫苗。
方法
我们进行了一项 1 期剂量发现研究，并正在对 6 个月至 11 岁健康儿童进行 BNT162b2 疫苗的持续 2 期-3 期安全性、免疫原性和疗效试验。我们报告了 6 个月至不到 2 岁和 2 至 4 岁儿童的数据截止日期（2022 年 4 月 29 日用于安全性和免疫原性，2022 年 6 月 17 日用于疗效）的结果。在 2 期-3 期试验中，参与者以 2:1 的比例随机分配接受两剂 3μg 的 BNT162b2 或安慰剂。根据初步免疫原性结果，从 2022 年 1 月开始，对第三剂 3μg（剂量 2 后≥8 周）进行了给药，这恰逢 B.1.1.529（奥密克戎）变体的出现。在 6 个月至不到 2 岁和 2 至 4 岁的儿童中，剂量 2 和 3 后 1 个月的免疫反应与在关键试验中接受 30μg BNT162b2 的 16 至 25 岁人群中剂量 2 后的免疫反应具有免疫桥接作用。
结果
在 1 期剂量发现研究中，16 名 6 个月至不到 2 岁的儿童（3μg 剂量）和 48 名 2 至 4 岁的儿童（3μg 或 10μg 剂量）接受了两剂 BNT162b2，间隔 21 天。选择 3μg 剂量水平用于 2 期-3 期试验；1178 名 6 个月至不到 2 岁的儿童和 1835 名 2 至 4 岁的儿童接受了 BNT162b2，分别有 598 名和 915 名接受了安慰剂。在两个年龄组中，1 个月后剂量 3 的几何平均比和血清反应的免疫桥接成功标准均得到满足。BNT162b2 的一般反应性事件主要为轻度至中度，无 4 级事件。接受 BNT162b2 （6 个月至<2 岁的儿童中为 7%，2 至 4 岁的儿童中为 5%）和安慰剂（6 至 7%的儿童中为 6 个月至<2 岁的儿童，4 至 5%的儿童中为 2 至 4 岁）后，报告的发热发生率较低且相似。在 6 个月至 4 岁的儿童中，观察到的针对有症状的 Covid-19 的总体疫苗效力为 73.2%（95%置信区间，43.8 至 87.6），从第 3 剂后 7 天开始（基于 34 例病例）。
结论
3μg BNT162b2 的三剂初级系列在 6 个月至 4 岁的儿童中是安全、免疫原性和有效的。（由 BioNTech 和辉瑞资助；临床试验编号，NCT04816643。）
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