Assessment of Anopheles salivary antigens as individual exposure biomarkers to species-specific malaria vector bites

Abstract

BackgroundMalaria transmission occurs during the blood feeding of infected anopheline mosquitoes concomitant with a saliva injection into the vertebrate host. In sub-Saharan Africa, most malaria transmission is due to Anopheles funestus s.s and to Anopheles gambiae s.l. (mainly Anopheles gambiae s.s. and Anopheles arabiensis). Several studies have demonstrated that the immune response against salivary antigens could be used to evaluate individual exposure to mosquito bites. The aim of this study was to assess the use of secreted salivary proteins as specific biomarkers of exposure to An. gambiae and/or An. funestus bites.MethodsFor this purpose, salivary gland proteins 6 (SG6) and 5′nucleotidases (5′nuc) from An. gambiae (gSG6 and g-5′nuc) and An. funestus (fSG6 and f-5′nuc) were selected and produced in recombinant form. The specificity of the IgG response against these salivary proteins was tested using an ELISA with sera from individuals living in three Senegalese villages (NDiop, n = 50; Dielmo, n = 38; and Diama, n = 46) that had been exposed to distinct densities and proportions of the Anopheles species. Individuals who had not been exposed to these tropical mosquitoes were used as controls (Marseille, n = 45).ResultsThe IgG responses against SG6 recombinant proteins from these two Anopheles species and against g-5′nucleotidase from An. gambiae, were significantly higher in Senegalese individuals compared with controls who were not exposed to specific Anopheles species. Conversely, an association was observed between the level of An. funestus exposure and the serological immune response levels against the f-5′nucleotidase protein.ConclusionThis study revealed an Anopheles salivary antigenic protein that could be considered to be a promising antigenic marker to distinguish malaria vector exposure at the species level. The epidemiological interest of such species-specific antigenic markers is discussed.

Purification of Plasmodium Sporozoites Enhances Parasite-Specific CD8 + T Cell Responses

“…It is tempting to postulate that APCs could be overwhelmed with mosquito-derived peptides, leading to mosquito-specific responses that self-regulate antigen-presenting DCs even as these APCs simultaneously present smaller quantities of parasite-derived antigens. Mosquito-derived antigens are known to induce antibody responses (54)(55)(56)(57), and both saliva and sporozoites remain in the skin for up to 18 h postbite (58).…”

Long-Lasting Permethrin-Impregnated Clothing Protects Against Mosquito Bites in Outdoor Workers

“…21,22 There have been a number of studies validating the detection of anti-mosquito salivary proteins as biomarkers for mosquito bite exposure. 21,[24][25][26][27][28][29][30] Although the different studies have all used different methods to assess immune response to mosquito salivary proteins, all suggest that antibodies to mosquito salivary proteins are effective biomarkers for exposure.…”

Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice

“…In contrast, persons from Senegal and Marseille had low IgG responses to AgTRIO, which were not significantly different. In addition, a previous study with these groups of sera has shown that individuals from Senegal had IgG responses to selected A. gambiae components, while persons from Marseille did not (Ali et al, 2012), further suggesting that AgTRIO is not highly antigenic during a natural mosquito bite.…”

“…Many studies have characterized mosquito salivary gland proteins using different techniques, including genomics, transcriptomic approaches, and proteomic approaches (Ali et al, 2012; Almeras et al, 2010; Arca et al, 2005, 2007; Calvo et al, 2004, 2009, 2010; Kalume et al, 2005; Valenzuela et al, 2003). Using a yeast surface display library from RNA isolated from female A. gambiae mosquitoes, and probing it with A. gambiae SGE antiserum, allows for the selection of antigens independent of the limits of detection due to protein quantity in saliva.…”