Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial
Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial
复制标题
DOI：
10.1016/s0140-6736(12)61854-6
复制
发表时间：
2013-01-19
期刊：
影响因子：
168.9
通讯作者：
Kilpi, Terhi M.
中科院分区：
文献类型：
--
作者：
Palmu, Arto A.;Jokinen, Jukka;Kilpi, Terhi M.
芬兰侵袭性肺炎球菌病（FinIP）疫苗试验旨在评估一种肺炎球菌疫苗的有效性，该疫苗含有10种与流感嗜血杆菌蛋白D、破伤风类毒素和白喉类毒素结合的肺炎球菌特异性多糖作为载体蛋白（PHiD-CV10）对抗侵袭性肺炎球菌疾病。方法在这项随机分组、双盲试验中，年龄小于19个月的儿童在52个集群中接受PHiD-CV10，或在26个集群中接受肝炎疫苗作为对照。首次接种时年龄小于7个月的婴儿接受3+1或2+1疫苗接种计划，7-11个月的儿童接受2+1计划，12-18个月的儿童接受两剂计划。主要和次要目的是在7月龄前接受至少一剂PHiD-CV10的儿童中，分别评估3+1和2+1方案的疫苗对培养证实的侵袭性肺炎球菌疾病的有效性。对肺炎球菌疾病的盲法随访从首次接种（2009年2月至2010年10月）持续至2012年1月31日。侵袭性疾病数据是从国家传染病登记册中积累的数据中检索的。该试验和巢式急性中耳炎试验分别在ClinicalTrials.gov注册，编号NCT 00861380和NCT 00839254。对30528名参与者进行了主要目标评估。检测到13例经培养确认的疫苗型侵袭性肺炎球菌疾病病例：PHiD-CV10 3+1组无，PHiD-CV10 2+1组1例，对照组12例。PHiD-CV10 3+1组和PHiD-CV10 2+1组的疫苗有效性估计值分别为100%（95% CI 83-100）和92%（58-100）。在合并的PHiD-CV10婴儿队列中检测到2例经培养证实的侵袭性疾病（无论血清型如何），而在相应的对照队列中检测到14例（疫苗有效性93%，75-99）。在随访队列中，报告了7例侵袭性疾病病例，均在对照组中：2例在7-11个月龄入组的儿童中; 5例在12-18个月龄入组的儿童中（疫苗有效性100%，79-100）。在18名儿童中，通过常规免疫后安全监测报告了疑似与疫苗相关的非致命严重不良事件。解释这项全国性试验显示，当以不同的时间表给予PHiD-CV10时，对侵袭性肺炎球菌疾病具有很高的有效性。这是第一次在临床试验中证实了2+1方案在婴儿中的有效性。
Background The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was designed to assess the effectiveness of a pneumococcal vaccine containing ten serotype-specific polysaccharides conjugated to Haemophilus influenzae protein D, tetanus toxoid, and diphtheria toxoid as the carrier proteins (PHiD-CV10) against invasive pneumococcal disease.Methods In this cluster-randomised, double-blind trial, children aged younger than 19 months received PHiD-CV10 in 52 clusters or hepatitis vaccines as control in 26 clusters. Infants aged younger than 7 months at the first vaccination received either a 3+1 or a 2+1 vaccination schedule, children aged 7-11 months received a 2+1 schedule, and those 12-18 months of age received a two-dose schedule. The primary and secondary objectives were to assess vaccine effectiveness against culture-confirmed invasive pneumococcal disease due to any of the ten vaccine serotypes for the 3+1 and 2+1 schedules, respectively, in children who received at least one PHiD-CV10 dose before 7 months of age. Masked follow-up of pneumococcal disease lasted from the first vaccination (from February, 2009, to October, 2010) to January 31, 2012. Invasive disease data were retrieved from data accumulated in the national infectious diseases register. This trial and the nested acute otitis media trial are registered with ClinicalTrials.gov, numbers NCT00861380 and NCT00839254, respectively.Findings 47 369 children were enrolled from February, 2009, to October, 2010. 30 528 participants were assessed for the primary objective. 13 culture-confirmed vaccine-type cases of invasive pneumococcal disease were detected: none in the PHiD-CV10 3+1 group, one in the PHiD-CV10 2+1 group, and 12 in the control groups. The estimates for vaccine effectiveness were 100% (95% CI 83-100) for PHiD-CV10 3+1 and 92% (58-100) for PHiD-CV10 2+1 groups. Two cases of any culture-confirmed invasive disease irrespective of serotype were detected in combined PHiD-CV10 infant cohorts compared with 14 in the corresponding control cohorts (vaccine effectiveness 93%, 75-99). In catch-up cohorts, seven cases of invasive disease were reported, all in the control group: two cases in the children enrolled at 7-11 months of age; and five cases in children enrolled at 12-18 months of age (vaccine effectiveness 100%, 79-100). Non-fatal serious adverse events suspected to be vaccine-related were reported via routine post-immunisation safety surveillance in 18 children.Interpretation This nationwide trial showed high PHiD-CV10 effectiveness against invasive pneumococcal disease when given in different schedules. For the first time, effectiveness of a 2+1 schedule in infants was confirmed in a clinical trial.