Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children:: randomised controlled trial
Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children:: randomised controlled trial
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DOI：
10.1016/s0140-6736(04)17223-1
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发表时间：
2004-10-16
期刊：
影响因子：
168.9
通讯作者：
Cohen, J
中科院分区：
文献类型：
--
作者：
Alonso, PL;Sacarlal, J;Cohen, J
研究背景研制有效的疟疾疫苗将极大地促进疾病控制。RTS，S/AS 02 A是基于恶性疟原虫环子孢子表面抗原的红细胞前疫苗候选物。我们的目的是评估疫苗的有效性，免疫原性和安全性在年轻的African children.Methods我们做了一个双盲，IIb期，随机对照试验在莫桑比克2022名儿童年龄1-4岁。这项研究包括生活在两个不同地区的两组儿童，他们接受了不同的后续计划。参与者被随机分配三剂RTS、S/AS 02 A候选疟疾疫苗或对照疫苗。在队列1（n=1605）中确定的主要终点是在6个月的监测期内至恶性疟原虫疟疾首次临床发作的时间（腋温大于或等于37.5 ℃和恶性疟原虫无性寄生虫血症>2500/穆尔）。在队列2（n=417）中确定了预防新发感染的疗效。结果队列1中的115名儿童和队列2中的50名儿童没有接受所有三种剂量，因此被排除在符合方案分析之外。首次临床发作的疫苗有效性为29.9%（95% CI 11.0-44.8; p=0.004）。在6个月观察期结束时，RTS，S/AS 02 A组的恶性疟原虫感染率比对照组低37%（11.9% VS 18.9%; p=0.0003）。疫苗对重症疟疾的有效性为57.7%（95% CI 16.2-80.6; p=0.019）。在队列2中，延长首次感染时间的疫苗有效性为45.0%（31.4-55.9; p
Background Development of an effective malaria vaccine could greatly contribute to disease control. RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on Plasmodium falciparum circumsporozoite surface antigen. We aimed to assess vaccine efficacy, immunogenicity, and safety in young African children.Methods We did a double-blind, phase IIb, randomised controlled trial in Mozambique in 2022 children aged 1-4 years. The study included two cohorts of children living in two separate areas which underwent different follow-up schemes. Participants were randomly allocated three doses of either RTS,S/AS02A candidate malaria vaccine or control vaccines. The primary endpoint, determined in cohort 1 (n=1605), was time to first clinical episode of P falciparum malaria (axillary temperature greater than or equal to37.5degreesC and P falciparum asexual parasitaemia >2500 per muL) over a 6-month surveillance period. Efficacy for prevention of new infections was determined in cohort 2 (n=417). Analysis was per protocol.Findings 115 children in cohort 1 and 50 in cohort 2 did not receive all three doses and were excluded from the perprotocol analysis. Vaccine efficacy for the first clinical episodes was 29.9% (95% CI 11.0-44.8; p=0.004). At the end of the 6-month observation period, prevalence of P falciparum infection was 37% lower in the RTS,S/AS02A group compared with the control group (11.9% VS 18.9%; p=0.0003). Vaccine efficacy for severe malaria was 57.7% (95% CI 16.2-80.6; p=0.019). In cohort 2, vaccine efficacy for extending time to first infection was 45.0 % (31.4-55.9; p