A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants
A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants
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DOI：
10.1056/nejmoa1208394
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发表时间：
2012-12-13
影响因子：
158.5
通讯作者：
Vansadia, Preeti
中科院分区：
文献类型：
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作者：
Mian-McCarthy, Sara;Agnandji, Selidji Todagbe;Vansadia, Preeti
在一项正在进行的3期试验中，候选疟疾疫苗RTS，S/AS 01使5至17个月儿童的临床和严重疟疾发作减少了约50%。我们研究了婴儿6至12周的年龄招募同一trial.METHODSWe管理RTS，S/AS 01或比较疫苗的6537名婴儿谁是6至12周的年龄在第一次接种时，与扩大免疫计划（EPI）疫苗在一个三剂每月计划。使用考克斯回归分析疫苗接种后12个月内首次或唯一一次临床疟疾发作的疫苗有效性（共同主要终点）。RTS、S/AS 01组在首次接种疫苗后14个月内，意向治疗人群中首次或唯一一次临床疟疾发作的发病率为0.31/人-年，对照组为0.40/人-年，疫苗有效性为30.1%（95%置信区间[ CI]，23.6 - 36.1）。符合方案人群的疫苗有效性为31.3%（97.5% CI，23.6 - 38.3）。在意向治疗人群中，疫苗对重症疟疾的有效性为26.0%（95%CI，-7.4至48.6），在符合方案人群中为36.6%（95%CI，4.6至57.7）。两个研究组中严重不良事件的发生频率相似。RTS，S/AS 01第三剂接种后1个月，99.7%的儿童抗环子孢子抗体阳性，几何平均滴度为209 EU/ml（95%CI，197 ~ 222）。结论RTS，S/AS 01疫苗与EPI疫苗联合接种对婴幼儿的临床和重症疟疾均有一定的保护作用。（由GlaxoSmithKline Biologicals和PATH疟疾疫苗倡议资助; RTS，S ClinicalTrials.gov编号，NCT 00866619。
BACKGROUNDThe candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial.METHODSWe administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed.RESULTSThe incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [ CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222).CONCLUSIONSThe RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.)