Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique:: a double blind randomised controlled phase I/IIb trial
Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique:: a double blind randomised controlled phase I/IIb trial
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DOI：
10.1016/s0140-6736(07)61542-6
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发表时间：
2007-11-03
期刊：
影响因子：
168.9
通讯作者：
Alonso, Pedro L.
中科院分区：
文献类型：
--
作者：
Aponte, John J.;Aide, Pedro;Alonso, Pedro L.
背景 疟疾仍然是一个主要的全球健康问题，需要改进现有干预措施的使用并加速开发新的控制方法。我们的目的是评估疟疾疫苗 RTS,S/AS02D 对非洲婴儿的安全性、免疫原性和初步疗效。方法我们对莫桑比克的 214 名婴儿进行了 I/IIb 期双盲随机试验。婴儿被随机分配在 10 周、14 周和 18 周龄时接受三剂 RTS、S/AS02D 或乙型肝炎疫苗 Engerix-B，并在 8、12 和 16 周龄时接受常规免疫疫苗。主要终点是研究前 6 个月内 RTS,S/AS02D 的安全性，分析是按意向治疗进行的。次要终点包括第三次给药后 3 个月随访期间的免疫原性和新恶性疟原虫感染的分析。使用 Cox 回归模型比较各组之间符合方案队列中出现新感染的时间。该研究已在 ClinicalTrials.gov 注册，编号为 NCT00197028。结果 每组中有 17 名儿童（15.9%；95% CI 9.5-24.2）出现严重不良事件。在截至2007年3月6日的随访中，RTS,S/AS02D组发生了31起严重不良事件，Engerix-B组发生了30起严重不良事件，但没有报告与疫苗接种有关。在同一随访期内，有四人死亡；所有受试者均在主动检测感染期后于研究第 6 个月结束（RTSS/AS02D 组有 2 例，Engerix-B 组有 2 例）。 RTS、S/AS02D 诱导高滴度的抗环子孢子抗体。记录了 68 例首次或仅有的恶性疟原虫感染：RTS、S/AS02D 组有 22 例，对照组有 46 例。调整后的疫苗效力为 65.9%（95% CI 42.6-79.8%，p
Background Malaria remains a leading global health problem that requires the improved use of existing interventions and the accelerated development of new control methods. We aimed to assess the safety, immunogenicity, and initial efficacy of the malaria vaccine RTS,S/AS02D in infants in Africa.Methods We did a phase I/IIb double-blind randomised trial of 214 infants in Mozambique. Infants were randomly assigned to receive three doses either of RTS,S/AS02D or the hepatitis B vaccine Engerix-B at ages 10 weeks, 14 weeks, and 18 weeks of age, as well as routine immunisation vaccines given at 8, 12, and 16 weeks of age. The primary endpoint was safety of the RTS,S/AS02D during the first 6 months of the study, and analysis was by intention to treat. Secondary endpoints included immunogenicity and analysis of new Plasmodium falciparum infections during a 3-month follow up after the third dose. Time to new infections in the per-protocol cohort were compared between groups using Cox regression models. This study is registered with ClinicalTrials.gov, number NCT00197028.Findings There were 17 children (15.9%; 95% CI 9.5-24.2) with serious adverse events in each group. In the follow-up which ended on March 6, 2007, there were 31 serious adverse events in the RTS,S/AS02D group and 30 serious adverse events in the Engerix-B group, none of which were reported as related to vaccination. There were four deaths during this same follow-up period; all of them after the active detection of infection period had finished at study month 6 (two in RTSS/AS02D group and two in the Engerix-B group). RTS,S/AS02D induced high titres of anti-circumsporozoite antibodies. 68 first or only P falciparum infections were documented: 22 in the RTS,S/AS02D group and 46 in the control group. The adjusted vaccine efficacy was 65.9% (95% CI 42.6-79.8%, p