The Anopheles gambiae gSG6 salivary protein: a serological marker of exposure to African malaria vectors.

With the final aim to develop novel additional tools for the evaluation of exposure to malaria vectors we started an analysis of the human humoral response to recombinant salivary proteins of the major African vector Anopheles gambiae. We started focusing our efforts on gSG6 (gambiae Salivary Gland protein 6), a small protein specifically expressed in adult female glands where it plays some important role in blood feeding (Lanfrancotti A et al., 2002; Arcà B et al., 2005; Lombardo F et al., 2009). This protein seemed especially suitable because it is relatively abundant in the An. gambiae saliva, is restricted to anopheline species and earlier studies indicated its immunogenicity to humans (Orlandi-Pradines E et al., 2007; Poinsignon A et al., 2008). We optimized conditions for expression and purification of a recombinant version of gSG6 and we used it to measure by ELISA the anti-gSG6 IgG response in human sera collected during three consecutive years in a rural malaria hyperendemic area of Burkina Faso. The IgG response in the exposed population varied according to malaria transmission and was short-lived, as indicated by a drop in the IgG levels during the dry low transmission season. The response started very early, with a maximum in one-two years old children, and then decreased according to age; a similar pattern has been previously observed with whole mosquito saliva (Peng Z et al., 2004) and interpreted as possible desensitization to salivary antigens. Interestingly, the response was significantly different in Mossi and Fulani, two sympatric ethnic groups already shown to differentially respond to several Plasmodium falciparum antigens (Modiano D et al., 1996; Torcia MG et al., 2008). An. gambiae, Anopheles arabiensis and Anopheles funestus are the three main African malaria vectors and they all carry in their saliva the SG6 protein. Since the An. arabiensis (aSG6) and the An. funestus (fSG6) homologues share 98% and 80% identities with gSG6, it is likely (although verification is needed) that the antibody response to gSG6 may be used to evaluate exposure to all three main African malaria vectors. In conclusion, our study provides strong support to the idea that anopheline-specific salivary antigens may represent a solid serological marker of exposure to malaria vectors and indicates that a reliable evaluation should also take into consideration the age and, if pertinent, the ethnic group of the populations analyzed. Moreover, comparative analysis of mosquito sialomes also highlights the existence of a relatively large group of culicine-specific salivary proteins suggesting their possible exploitation as indicators of exposure to Aedes and Culex vectors.