三抗原（前 S1/前 S2/S）乙型肝炎疫苗的有效性和安全性：俄罗斯联邦 III 期随机临床试验结果。
Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 Randomized Clinical Trial in the Russian Federation.
机构信息
Federal State Budgetary Educational Institution of Higher Education; Saint Petersburg State Paediatric Medical University of the Ministry of Health of the Russian Federation, Saint Petersburg, Russia.
St Petersburg State Budgetary Healthcare Institution; S.P. Botkin Clinical Infectious Diseases Hospital, Saint Petersburg, Russia.
出版信息
Clin Infect Dis. 2021 Nov 2;73(9):e3333-e3339. doi: 10.1093/cid/ciaa1649.
BACKGROUND
This study compares the immunogenicity and safety of a 3-antigen (S/pre-S1/pre-S2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia.
METHODS
We conducted a randomized, double-blind, comparative study of 3-dose regimens of 3AV (10 μg) and 1AV (20 µg) in adults aged 18-45 years. We evaluated immunogenicity based on hepatitis B surface (HBs) antibody titers at days 1, 28, 90, 180, and 210, adverse and serious adverse events (SAEs) to study day 210. The primary outcome was based on the difference in rates of seroconversion at day 210 (lower bound 95% confidence interval [CI]: > - 4%). Secondary outcomes were seroprotection rates (SPR), defined as anti-HBs ≥10 mIU/mL and anti-HBs geometric mean concentration (GMC).
RESULTS
Rate of seroconversion in 3AV (100%) was noninferior to 1AV (97.9%) at study day 210 (difference: 2.1%, 95% CI: -2.0, 6.3%]) but significantly higher at study day 28. SPR at study day 210 was >97% in both arms. Anti-HBs titers were significantly higher at study days 90 (P = .001) and 180 (P = .0001) with 3AV. Sex, age, and body mass index (BMI) had no impact on anti-HBs titers. The rates of local reactions related to vaccination were similar between vaccine arms (3AV vs 1AV) after the first (30% vs 18.8%, P = .15), second (20.0% vs 14.6%, P = .33), and third vaccination (14.9% vs 23.4%, P = .22). No SAEs were reported.
CONCLUSIONS
3AV was noninferior to 1AV. 3AV induced high SPR, and there were no safety concerns. Clinical Trials Registration. NCT04209400.
背景
本研究比较了三抗原（S/pre-S1/pre-S2）乙型肝炎（HepB）疫苗（3AV）与单抗原疫苗（1AV）在成人中的免疫原性和安全性，以支持 3AV 在俄罗斯的注册。
方法
我们进行了一项随机、双盲、对照的 3 剂方案研究，比较了 18-45 岁成人中 3AV（10 μg）和 1AV（20 μg）的免疫原性，根据乙肝表面（HBs）抗体滴度在第 1、28、90、180 和 210 天进行评估，以及在第 210 天发生的不良和严重不良事件（SAE）。主要结局基于第 210 天的血清转化率（下限 95%置信区间[CI]：＞-4%）差异。次要结局为血清保护率（SPR），定义为抗-HBs≥10 mIU/mL 和抗-HBs 几何平均浓度（GMC）。
结果
第 210 天 3AV（100%）的血清转化率非劣效于 1AV（97.9%）（差异：2.1%，95%CI：-2.0，6.3%），但在第 28 天显著更高。第 210 天的 SPR 在两个臂中均＞97%。第 90 天（P=0.001）和第 180 天（P=0.0001），3AV 的抗-HBs 滴度显著升高。性、年龄和体重指数（BMI）对抗-HBs 滴度无影响。接种后，与疫苗接种相关的局部反应率在两臂之间相似（第 1 针：30%比 18.8%，P=0.15；第 2 针：20.0%比 14.6%，P=0.33；第 3 针：14.9%比 23.4%，P=0.22）。未报告严重不良事件。
结论
3AV 非劣效于 1AV。3AV 诱导高 SPR，且无安全性担忧。临床试验注册。NCT04209400。
Zotero 插件