Wide cross-reactivity between Anopheles gambiae and Anopheles funestus SG6 salivary proteins supports exploitation of gSG6 as a marker of human exposure to major malaria vectors in tropical Africa

Abstract

BackgroundThe Anopheles gambiae gSG6 is an anopheline-specific salivary protein which helps female mosquitoes to efficiently feed on blood. Besides its role in haematophagy, gSG6 is immunogenic and elicits in exposed individuals an IgG response, which may be used as indicator of exposure to the main African malaria vector A. gambiae. However, malaria transmission in tropical Africa is sustained by three main vectors (A. gambiae, Anopheles arabiensis and Anopheles funestus) and a general marker, reflecting exposure to at least these three species, would be especially valuable. The SG6 protein is highly conserved within the A. gambiae species complex whereas the A. funestus homologue, fSG6, is more divergent (80% identity with gSG6). The aim of this study was to evaluate cross-reactivity of human sera to gSG6 and fSG6.MethodsThe A. funestus SG6 protein was expressed/purified and the humoral response to gSG6, fSG6 and a combination of the two antigens was compared in a population from a malaria hyperendemic area of Burkina Faso where both vectors were present, although with a large A. gambiae prevalence (>75%). Sera collected at the beginning and at the end of the high transmission/rainy season, as well as during the following low transmission/dry season, were analysed.ResultsAccording to previous observations, both anti-SG6 IgG level and prevalence decreased during the low transmission/dry season and showed a typical age-dependent pattern. No significant difference in the response to the two antigens was found, although their combined use yielded in most cases higher IgG level.ConclusionsComparative analysis of gSG6 and fSG6 immunogenicity to humans suggests the occurrence of a wide cross-reactivity, even though the two proteins carry species-specific epitopes. This study supports the use of gSG6 as reliable indicator of exposure to the three main African malaria vectors, a marker which may be useful to monitor malaria transmission and evaluate vector control measures, especially in conditions of low malaria transmission and/or reduced vector density. The Anopheles stephensi SG6 protein also shares 80% identity with gSG6, suggesting the attractive possibility that the A. gambiae protein may also be useful to assess human exposure to several Asian malaria vectors.

Detection of immunogenic proteins from Anopheles sundaicussalivary glands in the human serum

“…The same immunogenic proteins in different Anopheles mosquitoes, such as SG6, may trigger wide cross-reactivity between Anopheles species (31) . This universal characteristic of immunogenic proteins may improve their applicability as malaria vaccines in different regions.…”

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

“…The sera used for our human IgG response study had previously identified two Anopheles salivary protein candidates that are highly antigenic and potential biomarkers for exposure to mosquito bites (Ali et al, 2012). Several other studies have also identified such salivary protein candidates as biomarkers for exposure to mosquito bites and estimates of malaria transmission (Proietti et al, 2013; Rizzo et al, 2011, 2014; Stone et al, 2012; Ya-Umphan et al, 2017). The low IgG response to AgTRIO suggests a natural lack of antigenicity following mosquito exposure.…”

Anopheles salivary gland proteomes from major malaria vectors

“…funestus ). This cross-recognition could result from shared epitopes among these orthologous SG6 proteins [38,86]. According to their low molecular weights (approximately 11.7 and 13 kDa, respectively), gSG2 and gSG6 proteins should be contained in the large 11 kDa antigenic band detected in the Cellia subgenus.…”

“…These antibody responses were described as being short lived and linked to the level of exposure [28,30,31], highlighting the potential use of these responses to arthropod saliva antigens as immunological markers to evaluate individual exposure to arthropod bites [32] or assess the impact of vector control interventions [33]. Several studies demonstrated the presence of cross-reactive antibody responses against salivary proteins from different hematophagous arthropod species [34-38]. This cross-reactivity was attributed to the existence of antigens shared among different vector species [39].…”