GlaxoSmithKline, Wavre, Belgium.
GlaxoSmithKline, Rockville, MD, USA.
Lancet Infect Dis. 2019 Mar;19(3):287-297. doi: 10.1016/S1473-3099(18)30716-3. Epub 2019 Feb 11.
The duration of protection provided by varicella vaccines is unclear. We assessed the 10-year vaccine efficacy of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV), one live attenuated varicella vaccine (V) dose given after one measles-mumps-rubella vaccine (MMR) dose (MMR + V), versus two MMR doses (control vaccine) for the prevention of confirmed varicella.
This was a phase 3b follow-up of an observer-blinded, randomised, controlled trial. In phase a, children aged 12-22 months (at first vaccination) from Czech Republic (Czechia), Greece, Italy, Lithuania, Norway, Poland, Romania, Russia, Slovakia, and Sweden were randomly assigned by computer-generated randomisation list (3:3:1) to receive two doses of MMRV, one dose of MMR and one dose of varicella vaccine, or two doses of MMR, 42 days apart. Varicella cases were confirmed by detection of viral DNA, or epidemiological link and clinical assessment, by an independent data monitoring committee; disease severity was based on a modified Vázquez scale. Hazard ratios for MMRV and MMR + V versus MMR estimated in the per-protocol cohort using a Cox proportional hazards regression model were used to calculate vaccine efficacy and 95% CI. Serious adverse events were recorded throughout the study in all vaccinated children. Study objectives were secondary and descriptive. The trial is registered at ClinicalTrials.gov, number NCT00226499.
Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. The per-protocol cohort included 2279 children from the MMRV group, 2266 from the MMR + V group, and 744 from the MMR group. From baseline to a median follow-up of 9·8 years, 76 (3%) children in the MMRV group, 469 (21%) in the MMR + V group, and 352 (47%) in the MMR group had varicella. Vaccine efficacy against all varicella was 95·4% (95% CI 94·0-96·4) for MMRV and 67·2% (62·3-71·5) for MMR + V; vaccine efficacy against moderate or severe varicella was 99·1% (97·9-99·6) for MMRV and 89·5% (86·1-92·1) for MMR + V. During phase b, serious adverse events were reported by 290 (15%) of 1961 children in the MMRV group, 317 (16%) of 1978 in the MMR + V group, and 93 (15%) of 641 in the MMR group. There were no treatment-related deaths.
The 10-years vaccine efficacy observed, suggests that a two-dose schedule of varicella vaccine provided optimum long-term protection for the prevention of varicella by offering individual protection against all severities of disease and leading to a potential reduction in transmission, as observed in the US experience with universal mass vaccination.
GlaxoSmithKline Biologicals.
水痘疫苗的保护持续时间尚不清楚。我们评估了两剂麻疹-腮腺炎-风疹-水痘联合疫苗（MMRV）、一剂减毒活水痘疫苗（V）在一剂麻疹-腮腺炎-风疹疫苗（MMR）后接种（MMR+V），与两剂 MMR 疫苗（对照疫苗）在预防确诊水痘方面的 10 年疫苗效力。
这是一项为期 3b 期的观察者盲法、随机、对照试验的随访。在第 a 阶段，来自捷克共和国（捷克）、希腊、意大利、立陶宛、挪威、波兰、罗马尼亚、俄罗斯、斯洛伐克和瑞典的 12-22 个月龄儿童（首次接种时）按照计算机生成的随机列表（3:3:1）随机分配接受两剂 MMRV、一剂 MMR 和一剂水痘疫苗，或两剂 MMR，间隔 42 天。通过独立的数据监测委员会检测病毒 DNA 或流行病学联系和临床评估，确认水痘病例；疾病严重程度基于改良的 Vázquez 量表。使用 Cox 比例风险回归模型，对方案人群中的 MMRV 和 MMR+V 与 MMR 的估计进行风险比，以计算疫苗效力和 95%CI。在所有接种儿童中，整个研究期间均记录严重不良事件。研究目标是次要的和描述性的。该试验在 ClinicalTrials.gov 上注册，编号为 NCT00226499。
2005 年 9 月 1 日至 2006 年 5 月 10 日期间，5803 名儿童（平均年龄 14.2 个月，SD 2.5）接受了疫苗接种。方案人群包括 2279 名 MMRV 组、2266 名 MMR+V 组和 744 名 MMR 组儿童。从基线到中位数随访 9.8 年期间，MMRV 组有 76（3%）名儿童、MMR+V 组有 469（21%）名儿童和 MMR 组有 352（47%）名儿童发生水痘。MMRV 对所有水痘的疫苗效力为 95.4%（95%CI 94.0-96.4），MMR+V 为 67.2%（62.3-71.5）；MMRV 对中度或重度水痘的疫苗效力为 99.1%（97.9-99.6），MMR+V 为 89.5%（86.1-92.1）。在第 b 阶段，MMRV 组 1961 名儿童中有 290 名（15%）、MMR+V 组 1978 名儿童中有 317 名（16%）和 MMR 组 641 名儿童中有 93 名（15%）报告了严重不良事件。没有与治疗相关的死亡。
观察到的 10 年疫苗效力表明，水痘疫苗两剂方案为预防水痘提供了最佳的长期保护，可提供针对所有严重程度疾病的个体保护，并导致在美国普遍大规模接种疫苗时观察到的潜在传播减少。
葛兰素史克生物制品公司。
