Calculation of liver-to-blood inocula, parasite growth rates, and preerythrocytic vaccine efficacy, from serial quantitative polymerase chain reaction studies of volunteers challenged with malaria sporozoites
Calculation of liver-to-blood inocula, parasite growth rates, and preerythrocytic vaccine efficacy, from serial quantitative polymerase chain reaction studies of volunteers challenged with malaria sporozoites
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DOI：
10.1086/427243
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发表时间：
2005-02-15
影响因子：
6.4
通讯作者：
Hill, AVS
中科院分区：
文献类型：
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作者：
Bejon, P;Andrews, L;Hill, AVS
我们计算了候选红细胞前疟疾疫苗接种者和未接种疫苗的对照受试者中出现的恶性疟原虫寄生虫的数量和生长速度。这样做是为了测量疫苗的效力，并区分对血液阶段繁殖的影响和对肝脏阶段寄生虫的影响。寄生虫密度的实时聚合酶链反应测量值通过非线性回归和混合效应模型进行分析。肝脏寄生虫数量的显著减少是由于使用2种免疫方案：通过编码疟疾表位-血小板反应蛋白相关粘附蛋白插入物的修饰病毒Ankara（MVA）加强的FP 9（减少92%）和在异源初免-加强免疫方案中使用的RTS，S/AS 02，其中MVA编码环子孢子蛋白（减少97%）。对照受试者血液中的48小时生长率与任何疫苗接种组血液中的生长率均无差异（平均值，14.4倍[95%置信区间，11-19倍]）。
We calculated the number and growth rate of Plasmodium falciparum parasites emerging in recipients of candidate preerythrocytic malaria vaccines and unvaccinated control subjects undergoing mosquito-bite challenge. This was done to measure vaccine efficacy and to distinguish the effects on blood-stage multiplication from those on liver-stage parasites. Real-time polymerase chain reaction measurements of parasite densities were analyzed by nonlinear regression and mixed-effects models. Substantial reductions in numbers of liver parasites resulted from the use of 2 immunization regimens: FP9 boosted by modified virus Ankara (MVA) encoding the malaria epitope-thrombospondin-related adhesion protein insert (92% reduction) and RTS, S/AS02 used in heterologous prime-boost immunization regimens, with MVA encoding the circumsporozoite protein (97% reduction). Forty-eight-hour growth rates in blood from control subjects were not different from those in blood from any vaccination group (mean, 14.4-fold [95% confidence interval, 11-19- fold]).