Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
Parasit Vectors. 2017 Oct 17;10(1):489. doi: 10.1186/s13071-017-2414-z.
With the increasing interest in vaccines to interrupt malaria transmission, there is a demand for harmonization of current methods to assess Plasmodium transmission in laboratory settings. Potential vaccine candidates are currently tested in the standard membrane feeding assay (SMFA) that commonly relies on Anopheles stephensi mosquitoes. Other mosquito species including Anopheles gambiae are the dominant malaria vectors for Plasmodium falciparum in sub-Saharan Africa.
Using human serum and monoclonal pre-fertilization (anti-Pfs48/45) and post-fertilization (anti-Pfs25) antibodies known to effectively inhibit sporogony, we directly compared SMFA based estimates of transmission-reducing activity (TRA) for An. stephensi and An. gambiae mosquitoes.
In the absence of transmission-reducing antibodies, average numbers of oocysts were similar between An. gambiae and An. stephensi. Antibody-mediated TRA was strongly correlated between both mosquito species, and absolute TRA estimates for pre-fertilisation monoclonal antibodies (mAb) showed no significant difference between the two species. TRA estimates for IgG of naturally exposed individuals and partially effective concentrations of anti-Pfs25 mAb were higher for An. stephensi than for An. gambiae.
Our findings support the use of An. stephensi in the SMFA for target prioritization. As a vaccine moves through product development, better estimates of TRA and transmission-blocking activity (TBA) may need to be obtained in epidemiologically relevant parasite-species combination.
随着人们对疫苗中断疟疾传播的兴趣日益增加,需要协调当前在实验室环境中评估疟原虫传播的方法。目前正在标准膜 feeding 测定(SMFA)中测试潜在的疫苗候选物,该测定通常依赖于致倦库蚊。其他蚊种,包括冈比亚按蚊,是撒哈拉以南非洲地区恶性疟原虫的主要疟疾传播媒介。
使用已知可有效抑制孢子发生的人血清和单克隆预受精(抗 Pf48/45)和受精后(抗 Pf25)抗体,我们直接比较了基于 SMFA 的致倦库蚊和冈比亚按蚊传播减少活性(TRA)的估计值。
在没有传播减少抗体的情况下,冈比亚按蚊和致倦库蚊的卵囊数量相似。抗体介导的 TRA 与两种蚊种之间呈强相关性,并且两种蚊种的预受精单克隆抗体(mAb)的绝对 TRA 估计值没有显著差异。自然暴露个体的 IgG 和抗 Pf25 mAb 的部分有效浓度对致倦库蚊的 TRA 估计值高于冈比亚按蚊。
我们的研究结果支持在 SMFA 中使用致倦库蚊进行目标优先排序。随着疫苗通过产品开发,可能需要在与流行病学相关的寄生虫物种组合中获得更好的 TRA 和阻断传播活性(TBA)估计值。