The authors' affiliations are listed in the Appendix.
N Engl J Med. 2013 Dec 26;369(26):2481-91. doi: 10.1056/NEJMoa1215817. Epub 2013 Dec 11.
Commonly used trivalent vaccines contain one influenza B virus lineage and may be ineffective against viruses of the other B lineage. We evaluated the efficacy of a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages.
In this multinational, phase 3, observer-blinded study, we randomly assigned children 3 to 8 years of age, in a 1:1 ratio, to receive the QIV or a hepatitis A vaccine (control). The primary end point was influenza A or B confirmed by real-time polymerase chain reaction (rt-PCR). Secondary end points were rt-PCR-confirmed, moderate-to-severe influenza and rt-PCR-positive, culture-confirmed influenza. The vaccine efficacy and the effect of vaccination on daily activities and utilization of health care resources were assessed in the total vaccinated cohort (2584 children in each group) and the per-protocol cohort (2379 children in the QIV group and 2398 in the control group).
In the total vaccinated cohort, 62 children in the QIV group (2.40%) and 148 in the control group (5.73%) had rt-PCR-confirmed influenza, representing a QIV efficacy of 59.3% (95% confidence interval [CI], 45.2 to 69.7), with efficacy against culture-confirmed influenza of 59.1% (97.5% CI, 41.2 to 71.5). For moderate-to-severe rt-PCR-confirmed influenza, the attack rate was 0.62% (16 cases) in the QIV group and 2.36% (61 cases) in the control group, representing a QIV efficacy of 74.2% (97.5% CI, 51.5 to 86.2). In the per-protocol cohort, the QIV efficacy was 55.4% (95% CI, 39.1 to 67.3), and the efficacy against culture-confirmed influenza 55.9% (97.5% CI, 35.4 to 69.9); the efficacy among children with moderate-to-severe influenza was 73.1% (97.5% CI, 47.1 to 86.3). The QIV was associated with reduced risks of a body temperature above 39°C and lower respiratory tract illness, as compared with the control vaccine, in the per-protocol cohort (relative risk, 0.29 [95% CI, 0.16 to 0.56] and 0.20 [95% CI, 0.04 to 0.92], respectively). The QIV was immunogenic against all four strains. Serious adverse events occurred in 36 children in the QIV group (1.4%) and in 24 children in the control group (0.9%).
The QIV was efficacious in preventing influenza in children. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT01218308.).
常用的三价疫苗含有一种流感 B 病毒谱系，可能对另一种 B 谱系的病毒无效。我们评估了一种含有两种 B 谱系的候选灭活四价流感疫苗（QIV）的疗效。
在这项多中心、3 期、观察者设盲研究中，我们以 1:1 的比例随机分配 3 至 8 岁的儿童，分别接受 QIV 或甲型肝炎疫苗（对照）。主要终点是通过实时聚合酶链反应（rt-PCR）证实的甲型或乙型流感。次要终点是 rt-PCR 确诊的、中度至重度流感和 rt-PCR 阳性、培养阳性的流感。在总接种人群（每组 2584 名儿童）和方案人群（QIV 组 2379 名儿童和对照组 2398 名儿童）中评估了疫苗的疗效以及接种对日常活动和卫生保健资源利用的影响。
在总接种人群中，QIV 组 62 名（2.40%）和对照组 148 名（5.73%）儿童经 rt-PCR 确诊为流感，QIV 的疗效为 59.3%（95%可信区间[CI]，45.2 至 69.7），对培养阳性流感的疗效为 59.1%（97.5%CI，41.2 至 71.5）。对于中度至重度 rt-PCR 确诊的流感，QIV 组的发病率为 0.62%（16 例），对照组为 2.36%（61 例），QIV 的疗效为 74.2%（97.5%CI，51.5 至 86.2）。在方案人群中，QIV 的疗效为 55.4%（95%CI，39.1 至 67.3），对培养阳性流感的疗效为 55.9%（97.5%CI，35.4 至 69.9）；中度至重度流感患儿的疗效为 73.1%（97.5%CI，47.1 至 86.3）。与对照疫苗相比，在方案人群中，QIV 可降低体温高于 39°C 和下呼吸道疾病的风险（相对风险，0.29[95%CI，0.16 至 0.56]和 0.20[95%CI，0.04 至 0.92]）。QIV 对所有四种菌株均具有免疫原性。在 QIV 组中，36 名儿童（1.4%）和对照组 24 名儿童（0.9%）发生严重不良事件。
QIV 对预防儿童流感有效。（由葛兰素史克生物制品公司资助；临床试验.gov 编号，NCT01218308。）
