Anopheles gambiae salivary proteins: markers of exposure to anopheline mosquito?

Human immune response elicited by salivary proteins injected by Anopheles mosquitoes during blood-feeding may represent an indicator of exposure to anophelines and, therefore, a potential marker of malaria risk (Remoue F et al., 2006). Mosquito saliva is a complex cocktail of bioactive compounds, thus cross-reactivity to salivary antigens found in other mosquitoes (Aedes and/or Culex) or in other blood-sucking arthropods may be misleading. In this respect comparative transcriptome analysis revealed the presence of a large group of anopheline-specific proteins in the An. gambiae salivary repertoire (Arcà B et al., 2005; Ribeiro JMC et al., 2007). These Anopheles-specific proteins, if immunogenic, would represent ideal candidates as serological markers of exposure to bites of anopheline mosquitoes. With this aim, and in the framework of a more general effort of understanding the role of mosquito salivary proteins in parasite-vector-host interactions, we initiated the expression of selected An. gambiae salivary proteins to be assayed both for function and immunogenicity. We started choosing eight salivary proteins (gSG1, gSG5, gSG6, gSG7, gSG8, gVAG, cE5/Anophelin e hyp37.7) that are mainly or exclusively expressed in the female salivary glands of anopheline mosquitoes and whose functions are still unclear. So far five of these proteins have been successfully expressed in E. coli and/or in the yeast P. pastoris, with gSG6 being at the more advanced stage of purification/analysis. Knock-down by RNA interference suggests its involvement in blood-feeding; however, so far the specific function remained elusive. On the other side, as suggested by ELISA tests, gSG6 appears to be immunogenic and able to elicit an IgG response in the host. Preliminary assays with sera from exposed individuals from Burkina Faso showed a higher response in the Fulani ethnic group as compared to Mossi; however, no significant difference between Mossi and a control group was detected. Further analysis is in progress, including the use of gSG6-based peptides and the analysis of individuals from different epidemiological settings.