Antibody responses to gSG6-p1, AgSAP, and SAMSP1 following anopheline salivary exposure

Current methods to determine exposure to malaria-infected mosquitoes via entomologic investigations are technically challenging and can be inaccurate in low transmission settings. Antibody responses to mosquito salivary antigens (MSA) such as gSG6-p1 have been used as biomarkers of exposure to Anopheles mosquito bites, while newer MSA that are specifically associated with Plasmodium infection show promise for malaria vector exposure.

This study investigates two novel Anopheles gambiae salivary antigens, AgSAP and SAMSP1, as potential biomarkers of malaria vector exposure. We evaluated the humoral response to gSG6-p1, SAMSP1, and AgSAP in a murine model and in malaria-exposed individuals with submicroscopic parasitemia across different malaria endemicity areas, seasons, and infection statuses in coastal Tanzania. We also analyzed antibody kinetics following direct skin feeding assays carried out using uninfected colony-reared An. gambiae.

GSG6-p1, AgSAP, and SAMSP1 levels were all higher in individuals with submicroscopic malaria compared with endemic controls, and there was increased reactivity for AgSAP and gSG6-p1 in the villages with higher malaria prevalence, though most of these findings were only borderline significant. Meanwhile, SAMSP1 was the only MSA that induced a significantly higher humoral response during the rainy season, perhaps due to greater sequence identity of this MSA across multiple Anopheles species. GSG6-p1, AgSAP, and SAMSP1 levels increased in mice at 8 weeks after weekly mosquito feedings. However, human gSG6-p1 and AgSAP levels were paradoxically lower 4 weeks after direct skin feeding assays.

Mosquito salivary antigens associated with Plasmodium infection such as AgSAP and SAMSP1 show promise as biomarkers of malaria vector exposure. However, the dynamics of immunoglobulin (Ig)G response against AgSAP and SAMSP1 after mosquito bites requires further study.