Poinsignon Anne, Cornelie Sylvie, Mestres-Simon Montserrat, Lanfrancotti Alessandra, Rossignol Marie, Boulanger Denis, Cisse Badara, Sokhna Cheikh, Arcà Bruno, Simondon François, Remoue Franck
UR024-Epidémiologie et Prévention, Institut de Recherche pour le Développement, Dakar, Sénégal.
PLoS One. 2008 Jun 25;3(6):e2472. doi: 10.1371/journal.pone.0002472.
In order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites.
METHODOLOGY/PRINCIPAL FINDINGS: Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i) their potential antigenic properties and ii) the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1.
CONCLUSIONS/SIGNIFICANCE: This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing techniques, for mapping the risk of malaria. It could also represent a direct criterion of efficacy in evaluation of vector control strategies.
为了加强疟疾防控,并在世卫组织建议的支持下,人们正在致力于开发新工具,以识别寄生虫传播高风险的地理区域。评估人体对节肢动物唾液蛋白的抗体反应可能是接触媒介叮咬进而接触病原体传播风险的一种流行病学指标。就仅由按蚊传播的疟疾而言,通过鉴定按蚊属特有的免疫原性蛋白可实现最大特异性。本研究的目的是确定针对冈比亚按蚊gSG6蛋白从重组形式到衍生合成肽的IgG反应是否可能是冈比亚按蚊叮咬特异性接触的免疫标志物。
方法/主要发现:在生活于疟疾流行的塞内加尔地区的儿童中观察到了针对重组gSG6蛋白的特异性IgG抗体。为了优化按蚊特异性和可重复性,我们采用生物信息学方法设计了五个基于gSG6的肽序列,同时考虑到:i)它们潜在的抗原特性;ii)与其他节肢动物/生物体的蛋白质序列无交叉反应性。在接触过疟疾的儿童中评估了特异性抗肽IgG抗体反应。这五个gSG6肽表现出不同的抗原特性,其中gSG6-P1和gSG6-P2的抗原性最高。然而,仅gSG6-P1在雨季特异性IgG反应显著增加,且IgG水平与冈比亚按蚊叮咬接触水平呈正相关。
结论/意义:这种逐步推进的方法表明,gSG6-P1可能是评估冈比亚按蚊叮咬接触情况的最佳候选标志物。该标志物可作为一种地理指标,像遥感技术一样,用于绘制疟疾风险图。它还可能代表评估病媒控制策略效果的直接标准。