带状疱疹亚单位佐剂疫苗在老年人中相隔 2、6 或 12 个月接种 2 剂的免疫原性、反应原性和安全性：III 期、随机、开放标签、多中心研究结果。
Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: Results of a phase III, randomized, open-label, multicenter study.
机构信息
GSK, 709 Swedeland Road, King of Prussia, PA 19406, USA.
Kliiniliste Uuringute Keskus, 54 Sobra, 50160 Tartu, Estonia.
出版信息
Vaccine. 2018 Jan 2;36(1):148-154. doi: 10.1016/j.vaccine.2017.11.019. Epub 2017 Nov 22.
BACKGROUND
In phase III trials, 2 doses of a herpes zoster (HZ) subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01 Adjuvant System) administered 2-months apart in older adults (≥50 and ≥70 years) demonstrated >90% efficacy in preventing HZ and had a clinically acceptable safety profile. Here we report immunogenicity, reactogenicity and safety following administration of 2 HZ/su doses at intervals longer than 2 months.
METHODS
In this Phase III, open-label trial conducted in the US and Estonia, 354 adults ≥50 years were randomized 1:1:1 to receive 2 HZ/su doses 2, 6, or 12 months apart. gE-specific humoral immune responses were evaluated at pre-vaccination, 1 and 12 months post-dose 2. Co-primary objectives were to compare immune responses to HZ/su 1 month post-dose 2 when given 6-months or 12-months apart to those administered 2-months apart. For each participant, safety information was collected from dose 1 to 12 months post-dose 2.
RESULTS
346 participants completed the study and 343 were included in the according-to-protocol cohort for immunogenicity. One month post-dose 2, vaccine response rates were 96.5% (97.5% confidence interval [CI]: 90.4; 99.2) and 94.5% (97.5% CI: 87.6; 98.3) for the 0, 6- and 0, 12-month schedules, respectively, both schedules meeting the pre-defined criterion. Non-inferiority of anti-gE geometric mean concentrations was demonstrated for HZ/su administered on 0, 6-month compared to a 0, 2-month schedule; however, HZ/su administered on a 0, 12-month schedule did not meet the non-inferiority criterion. Injection site pain was the most commonly reported solicited adverse event (AE). 26 participants each reported at least 1 serious AE; none were assessed as related to vaccination.
CONCLUSIONS
Immune responses to HZ/su administered at 0, 6-month were non-inferior to those elicited by a 0, 2-month schedule. HZ/su exhibited a clinically acceptable safety profile for all dosing intervals.
CLINICAL TRIALS REGISTRATION
Clinicaltrials.gov (NCT01751165).
背景
在 III 期临床试验中，在年龄较大的成年人（≥50 岁和≥70 岁）中，间隔 2 个月给予 2 剂带状疱疹（HZ）亚单位疫苗（HZ/su；50μg 水痘带状疱疹病毒糖蛋白 E [gE]和 AS01 佐剂系统），预防 HZ 的疗效超过 90%，且具有可接受的临床安全性。在此，我们报告了在间隔超过 2 个月的情况下，接受 2 剂 HZ/su 后免疫原性、反应原性和安全性。
方法
在这项在美国和爱沙尼亚进行的 III 期、开放标签试验中，354 名年龄≥50 岁的成年人按 1:1:1 的比例随机接受间隔 2、6 或 12 个月的 2 剂 HZ/su。在接种疫苗前、接种后 1 个月和 12 个月时评估 gE 特异性体液免疫应答。主要共同终点是比较间隔 6 个月或 12 个月给予 2 剂 HZ/su 后 1 个月时的免疫应答与间隔 2 个月给予的免疫应答。对于每个参与者，从接种第 1 剂到接种第 2 剂后 12 个月收集安全性信息。
结果
346 名参与者完成了研究，343 名参与者被纳入符合方案的免疫原性队列。接种后 1 个月，0、6 个月和 0、12 个月方案的疫苗应答率分别为 96.5%（97.5%置信区间[CI]：90.4；99.2）和 94.5%（97.5% CI：87.6；98.3），均符合预先定义的标准。与 0、2 个月方案相比，0、6 个月方案的抗-gE 几何平均浓度具有非劣效性；然而，0、12 个月方案的 HZ/su 未达到非劣效性标准。注射部位疼痛是最常见的报告不良事件（AE）。每个方案各有 26 名参与者报告了至少 1 例严重 AE；均未评估为与疫苗接种相关。
结论
间隔 6 个月给予 HZ/su 的免疫应答与间隔 2 个月方案相当。在所有给药间隔，HZ/su 具有可接受的临床安全性。
临床试验注册
Clinicaltrials.gov（NCT01751165）。
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