Randomized Controlled Trial of RTS,S/AS02D and RTS,S/AS01E Malaria Candidate Vaccines Given According to Different Schedules in Ghanaian Children
Randomized Controlled Trial of RTS,S/AS02D and RTS,S/AS01E Malaria Candidate Vaccines Given According to Different Schedules in Ghanaian Children
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DOI：
10.1371/journal.pone.0007302
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发表时间：
2009-10-02
期刊：
影响因子：
3.7
通讯作者：
Evans, Jennifer
中科院分区：
文献类型：
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作者：
Owusu-Agyei, Seth;Ansong, Daniel;Evans, Jennifer
背景：在非洲疟疾流行国家，S候选疟疾疫苗的目标交付渠道是世界卫生组织扩大免疫计划。作为一种辅助系统、年龄降级和方案选择步骤，本研究评估了S/AS01(E)和S/AS02(D)三种方案在加纳5-17个月婴幼儿中的应用。方法：于2006年8月至2008年5月在加纳的两(2)个中心进行了为期19个月的II期随机对照研究(对疫苗盲目，不按方案)。受试者被随机分配到每个研究地点的六个研究组中的一个(1：1：1：1：1：1)，每个研究组都定义了应该接种哪种疫苗以及按照哪个时间表(0、1-、0、1、2-或0、1、7个月)。对于0、1、2个月的计划，参与者在一个中心接种RTS、S/AS01(E)或狂犬病疫苗，另一个中心接种RTS、S/AS01(E)或RTS、S/AS02(D)。对于两个研究地点的其他时间表，他们接受RTS，S/AS01(E)或RTS，S/AS02(D)。主要的结果衡量标准是服药后10个月前严重不良事件的发生率。结果：各组报告的严重不良事件数量是平衡的。1名儿童出现单纯性热性惊厥，病情进展顺利，无后遗症，认为与接种S/AS01E疫苗有关。与狂犬病疫苗相比，接受RTS、S/AS疫苗的受者发生低级别反应的频率略高；3级反应发生的频率较低。RTS，S/AS01(E)的局部反应性低于RTS，S/AS02(D)。两种候选疫苗对抗环子孢子和抗乙肝病毒表面抗原抗体均具有较强的免疫原性。与RTS相比，S/AS0 1(E)和S/AS0 2(D)在3个方案中的抗环子孢子抗体峰值均较高。3个给药方案比2个给药方案更具免疫原性。抗环子孢子抗体曲线下面积分析在0，1，2和0，1，7个月的RTS，S/AS01(E)方案之间具有可比性。结论：两种候选疟疾疫苗耐受性良好。在给药3次时，S/AS01(E)组的抗环子孢子有效率明显高于S/AS02(D)组。这项研究支持选择RTS、S/AS01E和3剂量时间表以促进儿童和婴儿的进一步发育。
Backgroud: The target delivery channel of RTS,S candidate malaria vaccines in malaria-endemic countries in Africa is the World Health Organisation Expanded Program on Immunization. As an Adjuvant System, age de-escalation and schedule selection step, this study assessed 3 schedules of RTS,S/AS01(E) and RTS,S/AS02(D) in infants and young children 5-17 months of age in Ghana.Methodology: A Phase II, partially-blind randomized controlled study (blind to vaccine, not to schedule), of 19 months duration was conducted in two (2) centres in Ghana between August 2006 and May 2008. Subjects were allocated randomly (1:1:1:1:1:1) to one of six study groups at each study site, each defining which vaccine should be given and by which schedule (0,1-, 0,1,2- or 0,1,7-months). For the 0,1,2-month schedule participants received RTS,S/AS01(E) or rabies vaccine at one center and RTS,S/AS01(E) or RTS,S/AS02(D) at the other. For the other schedules at both study sites, they received RTS,S/AS01(E) or RTS,S/AS02(D). The primary outcome measure was the occurrence of serious adverse events until 10 months post dose 1.Results: The number of serious adverse events reported across groups was balanced. One child had a simple febrile convulsion, which evolved favourably without sequelae, considered to be related to RTS, S/AS01E vaccination. Low grade reactions occurred slightly more frequently in recipients of RTS,S/AS than rabies vaccines; grade 3 reactions were infrequent. Less local reactogenicity occurred with RTS,S/AS01(E) than RTS,S/AS02(D). Both candidate vaccines were highly immunogenic for anti-circumsporozoite and anti-Hepatitis B Virus surface antigen antibodies. Recipients of RTS,S/AS01(E) compared to RTS,S/AS02(D) had higher peak anti-circumsporozoite antibody responses for all 3 schedules. Three dose schedules were more immunogenic than 2 dose schedules. Area under the curve analyses for anti-circumsporozoite antibodies were comparable between the 0,1,2- and 0,1,7-month RTS,S/AS01(E) schedules.Conclusions: Both candidate malaria vaccines were well tolerated. Anti-circumsporozoite responses were greater with RTS,S/AS01(E) than RTS,S/AS02(D) and when 3 rather than 2 doses were given. This study supports the selection of RTS, S/AS01E and a 3 dose schedule for further development in children and infants.