A field trial to assess a blood-stage malaria vaccine.
A field trial to assess a blood-stage malaria vaccine.
复制标题
DOI：
10.1056/nejmoa1008115
复制
发表时间：
2011-09-15
期刊：
影响因子：
--
通讯作者：
Plowe CV
中科院分区：
文献类型：
--
作者：
Thera MA;Doumbo OK;Coulibaly D;Laurens MB;Ouattara A;Kone AK;Guindo AB;Traore K;Traore I;Kouriba B;Diallo DA;Diarra I;Daou M;Dolo A;Tolo Y;Sissoko MS;Niangaly A;Sissoko M;Takala-Harrison S;Lyke KE;Wu Y;Blackwelder WC;Godeaux O;Vekemans J;Dubois MC;Ballou WR;Cohen J;Thompson D;Dube T;Soisson L;Diggs CL;House B;Lanar DE;Dutta S;Heppner DG Jr;Plowe CV
血液阶段疟疾疫苗旨在预防临床疾病。疟疾疫苗FMP2.1/AS 02 A是一种基于恶性疟原虫3D 7株顶端膜抗原1（AMA 1）的重组蛋白，此前已被证明在马里成人和儿童中具有免疫原性和可接受的安全性。在一项双盲随机试验中，我们用疟疾疫苗或对照（狂犬病）疫苗对400名马里儿童进行了免疫接种，并对他们进行了6个月的随访。主要终点是临床疟疾，定义为发热和每立方毫米血液中至少2500个寄生虫。次要终点是由疫苗株中发现的AMA 1 DNA序列的寄生虫引起的临床疟疾。主要终点的累积发生率在疟疾疫苗组为48.4%，对照组为54.4%;主要终点的有效性为17.4%（主要终点的风险比为0.83; 95%置信区间[CI]为0.63 - 1.09; P = 0.18）。根据各种寄生虫密度阈值，对首次和随后的临床疟疾发作的疗效约为20%。对由具有与疫苗株对应的AMA 1的寄生虫引起的临床疟疾的有效性为64.3%（风险比，0.36; 95%CI，0.08至0.86; P = 0.03）。接种疟疾疫苗后的局部反应和发烧更常见。根据主要终点，疟疾疫苗对临床疟疾没有显著的保护作用，但根据次要结果，它可能具有株特异性效力。如果这一发现得到证实，AMA 1可能用于多组分疟疾疫苗。
Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02A, a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children. In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain. The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P = 0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P = 0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine. On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine.