Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom.
PLoS One. 2011;6(7):e22271. doi: 10.1371/journal.pone.0022271. Epub 2011 Jul 22.
Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria.
In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes.
A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = -0.93 [95% CI: -1.0, -0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = -0.93 [95% CI: -0.99, -0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5-9], control group median 9 days [range 7-9]).
Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers.
ClinicalTrials.gov [NCT00984763].
抑制寄生虫生长是血阶段疟疾疫苗的主要目标。寄生虫生长抑制活性（GIA）的体外测定广泛用作疟疾疫苗功效的替代标志物，用于候选血阶段疫苗的降选。在这里，我们报告了第一项研究，该研究检查了人类体内疟原虫生长率与体外 GIA 之间的关系，这些人是通过实验性感染血阶段疟疾的。
在这项 I/IIa 期开放标签临床试验中，五名健康的无疟疾志愿者接种了 AMA1/C1-Alhydrogel+CPG 7909，并与三名未接种疫苗的对照者一起通过静脉内接种感染的疟原虫红细胞进行了挑战。
在 48 小时内观察到寄生虫倍增率（PMR）与疫苗诱导的生长抑制活性之间存在显著相关性（Pearson r=-0.93[95%CI：-1.0，-0.27]P=0.02）和 AMA1 抗体滴度在疫苗组中（Pearson r=-0.93[95%CI：-0.99，-0.25]P=0.02）。然而，与对照组相比，免疫接种未能降低疫苗组的总体平均 PMR（疫苗接种者 16 倍[95%CI：12,22]，对照组 17 倍[CI：0,65]P=0.70）。因此，未观察到潜伏前期的影响（疫苗组中位数 8.5 天[范围 7.5-9]，对照组中位数 9 天[范围 7-9]）。
尽管在人类实验性疟疾感染中首次观察到疫苗诱导的体外生长抑制活性与体内寄生虫倍增率之间存在显著关联，但这并未转化为该小志愿者组中任何可观察到的临床相关疫苗效应。
ClinicalTrials.gov[NCT00984763]。
