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

被引:389
作者
Genton, B
Betuela, I
Felger, I
Al-Yaman, F
Anders, RF
Saul, A
Rare, L
Baisor, M
Lorry, K
Brown, GV
Pye, D
Irving, DO
Smith, TA
Beck, HP
Alpers, MP
机构
[1] Swiss Trop Inst, CH-4002 Basel, Switzerland
[2] Papua New Guinea Inst Med Res, Maprik, Papua N Guinea
[3] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
[4] CSL, Melbourne, Vic, Australia
[5] Queensland Inst Med Res, Brisbane, Qld 4006, Australia
[6] Cooperat Res Ctr Vaccine Technol, Brisbane, Qld, Australia
[7] Biotech Australia, Sydney, NSW, Australia
关键词
D O I
10.1086/339342
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:820 / 827
页数:8
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