Human IgG response to the Anopheles gambiae salivary protein gSG6: an indicator of exposure to anopheline mosquito bites.

The ability to estimate the risk of malaria infection is crucial for the development and evaluation of control programmes and currently relies on both entomological and parasitological methods. The availability of rapid and sensitive tools to measure the exposure to Anopheles mosquito bites would be extremely valuable in this context. Human antibody response to Anopheles saliva may represent such an indicator (Remoue F et al, 2006, Trans R Soc Trop Med Hyg). However, mosquito saliva is a complex cocktail of bioactive factors and cross-reactivity with other antigens (i.e. salivary proteins from blood-feeders other than anophelines) may be misleading. In the attempt to identify immunogenic and anopheline-specific proteins to be used as serological indicators of exposure to malaria vectors we focused our attention on the Anopheles gambiae gSG6. This is a small, female salivary gland-specific protein involved in blood feeding (Lombardo F et al, 2009, Insect Biochem Mol Biol). So far, gSG6 has been found only in anopheline species (An. gambiae complex, An. stephensi, An. funestus and An. freeborni) whereas it is absent in culicine mosquitoes and in other blood feeding arthropods. Previous studies suggested that gSG6 is immunogenic (Poinsignon A et al, 2008, PLoS One) and, therefore, we expressed the protein in recombinant form and measured the humoral immune response to gSG6 in human sera collected during three consecutive years in rural malaria hyperendemic areas of Burkina Faso. gSG6 was confirmed to be immunogenic and to elicit an IgG response that varies according to malaria transmission intensity. Interestingly, a significant decrease in the IgG levels was observed during the dry season, suggesting that this response is short-lived. Moreover, anti-gSG6 IgG levels differed significantly in the two sympatric ethnic groups, Mossi and Fulani, already known for their differential response to several P. falciparum antigens (Modiano D et al, 1996, Proc Natl Acad Sci USA). Finally, the IgG response varied with age, being higher in children and progressively decreasing in older people. This decline suggests the possible involvement of a mechanism of tolerance developed as consequence of a continued exposure to the antigen. The high level of anti-gSG6 IgG4 found in the sera of exposed individuals appears compatible with the implication of a desensitization mechanism. Overall, our study provides a solid indication that individual recombinant salivary proteins may represent useful tools for epidemiological studies, evaluation of vector-control campaigns and perhaps for the development of risk maps. (*equal contribution)