RTS,S/AS01 疟疾疫苗在非洲婴儿中的 3 期临床试验。
A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants.
机构信息
Albert Schweitzer Hospital, Lambaréné, Gabon.
出版信息
N Engl J Med. 2012 Dec 13;367(24):2284-95. doi: 10.1056/NEJMoa1208394. Epub 2012 Nov 9.
BACKGROUND
The 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.
METHODS
We 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.
RESULTS
The 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).
CONCLUSIONS
The 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.).
背景
在一项正在进行的 3 期临床试验中，候选疟疾疫苗 RTS,S/AS01 可将 5 至 17 月龄儿童的临床和重度疟疾发作减少约 50%。我们研究了同一试验招募的 6 至 12 周龄婴儿。
方法
我们给 6537 名 6 至 12 周龄婴儿接种了 RTS,S/AS01 或对照疫苗，这些婴儿在第一次接种疫苗时同时接受了扩大免疫规划（EPI）疫苗，接种方案为每月 3 剂。使用 Cox 回归分析疫苗对接种后 12 个月内首次或唯一临床疟疾发作的疗效（主要复合终点）。还评估了疫苗对所有疟疾发作的疗效、疫苗对重度疟疾的疗效、安全性和免疫原性。
结果
在接受意向治疗人群中，在首次接种疫苗后 14 个月内，RTS,S/AS01 组的第一个或唯一临床疟疾发作率为 0.31 人年，对照组为 0.40 人年，疫苗效力为 30.1%（95%置信区间[CI]，23.6 至 36.1）。在方案人群中，疫苗效力为 31.3%（97.5%CI，23.6 至 38.3）。在接受意向治疗的人群中，疫苗对重度疟疾的疗效为 26.0%（95%CI，-7.4 至 48.6），在按方案人群中为 36.6%（95%CI，4.6 至 57.7）。两组研究人群发生严重不良事件的频率相似。在接种 RTS,S/AS01 第三剂后 1 个月，99.7%的儿童抗环子孢子蛋白抗体阳性，几何平均滴度为每毫升 209 EU（95%CI，197 至 222）。
结论
与 EPI 疫苗联合使用的 RTS,S/AS01 疫苗对婴幼儿的临床和重度疟疾提供了适度的保护。（由葛兰素史克生物制品公司和 PATH 疟疾疫苗倡议资助；RTS,S 临床试验注册编号，NCT00866619。）
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