Novel Peptide Marker Corresponding to Salivary Protein gSG6 Potentially Identifies Exposure to Anopheles Bites

Abstract

BackgroundIn 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 FindingsSpecific 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/SignificanceThis 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.

Human Antibody Response to Anopheles gambiae Saliva: An Immuno-Epidemiological Biomarker to Evaluate the Efficacy of Insecticide-Treated Nets in Malaria Vector Control

“…Indeed, this kind of Ab immunity does not seem to accumulate with exposure during individual life but wanes rapidly, even with sustained exposure. 28,33 Nevertheless, these preliminary results according to age have to be confirmed, but they suggest that the use of this "saliva" biomarker could be relevant at all ages; this enhances the relevance of this indicator, because it is also suggested in other areas. 31 Deltamethrin, like most pyrethroid insecticides, has a powerful repulsive effect and is an effective mosquito killer (knockdown effect), but resistance has spread in the last decade in Africa.…”

“…gambiae gSG6 protein, is proving to be a reliable immuno-epidemiological marker of the intensity of Anopheles exposure. 33 The evaluation of anti-gSG6-P1 IgG response as a marker of ITN efficacy could be planned in the same studied population.…”

Human Antibody Response to Aedes aegypti Saliva in an Urban Population in Bolivia: A New Biomarker of Exposure to Dengue Vector Bites

“…gambiae. 34,37 The sialome of Ae. aegypti is currently being investigated by using an immuneproteomic approach to define antigenic candidates for a specific, sensitive, and reproducible biomarker of exposure to Ae.…”

Biomarkers for susceptibility to infection and disease severity in human malaria

“…The practical large-scale application of serological tests to detect vector salivaspecific antibodies for epidemiological purposes has been hampered by the difficulty in obtaining sufficient quantities of vector saliva and by problems in the standardisation of the reagent. Recently, the feasibility of using peptide markers to identify exposure to Anopheles bites has been demonstrated (Poinsignon et al 2008a). …”