Differential humoral response to the Anopheles gambiae gSG6 and cE5 salivary proteins in a malaria hyperendemic area of Burkina Faso

We previously reported that the An. gambiae salivary protein gSG6 may be exploited as marker of human exposure to the three main Afrotropical malaria vectors: An. gambiae, An. arabiensis and An. funestus [1,2]. We recently characterized the An. gambiae salivary protein cE5, a highly specific thrombin inhibitor of the anophelin family [3], and we report here the comparative analysis of the humoral response to gSG6 and cE5 in a group of individuals from a malaria hyperendemic area of Burkina Faso. Despite the individual heterogeneity cE5 was more immunogenic than gSG6. Consistently with a previous report [1] the anti-gSG6 IgG response decreased with age, whereas the anti-cE5 humoral response showed a trend to increase during adulthood. Intriguingly, the humoral response to these two proteins also differed for the dominant IgG subclass: IgG4>IgG1 for gSG6, and IgG1>>IgG4 for cE5. IgG1 and IgG4 are usually considered as markers of Th1- and Th2-type responses, respectively. Therefore, we identified two salivary antigens with different antigenic properties: (i) gSG6, which seems to triggers a Th2-type response, with high IgG4 levels and induction of tolerance; (ii) cE5, apparently eliciting a Th1-type response, with high IgG1 levels and no development of tolerance. Previous reports in murine malaria models indicated that pre-immunization with Anopheles saliva may provide protection from Plasmodium infection by up-regulation of Th1-type response [4, 5]. In this context the An. gambiae gSG6 and cE5 salivary proteins may represent useful tools to study both the effects of mosquito saliva on early host response to Plasmodium infection and the mechanisms underlying the development of tolerance to insect saliva. [1] Rizzo C et al, 2011 PLoS ONE; [2] Rizzo C et al, 2011, Malaria J; [3] Ronca R et al, 2012 submitted; [4] Donovan MJ et al, 2007 Infect Immun; [5] Fonseca L et al, 2007 Malaria J.