A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea
A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea
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DOI：
10.1086/339342
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发表时间：
2002-03-15
影响因子：
6.4
通讯作者：
Alpers, MP
中科院分区：
文献类型：
--
作者：
Genton, B;Betuela, I;Alpers, MP
疟疾疫苗组合B包含在油基佐剂中配制的重组恶性疟原虫环感染的红细胞表面抗原和2种裂殖子表面蛋白（MSP 1和MSP 2）。一项在巴布亚新几内亚120名儿童（5-9岁）中进行的1-2b期双盲、随机、安慰剂对照试验表明，未接受磺胺嘧啶-乙胺嘧啶预处理的儿童的寄生虫密度降低了62%（95%置信限：13%，84%）。接种者携带MSP 2 - 3D 7等位基因形式的寄生虫的患病率较低（对应于疫苗中的等位基因形式），与FC 27型寄生虫相关的病态发作的发生率较高。这些结果证明了组合B在先前有疟疾暴露的个体中抗恶性疟原虫的功能活性。对具有特定msp 2基因型的寄生虫的特定作用表明，MSP 2组分至少部分地解释了活性。施加在寄生虫上的疫苗诱导的选择压力及其对发病率的后果强烈主张开发包含保守抗原和/或覆盖所有重要等位基因类型的多个组分的疫苗。
The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic types.