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Antibody responses to SG6, AgSAP, and SAMSP1 following Anopheline salivary exposure

Williams, R. J.; Swinehart, B. D.; Abouneameh, S.; Rutha, I. J.; Msolo, D. C.; Tarimo, B.; Fikrig, E.; Mathias, D.; Ngasala, B.; Chuang, Y.-M.; Lin, J. T.

2025-07-15 infectious diseases
10.1101/2025.07.14.25331506 medRxiv
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BackgroundCurrent 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) like gSG6-P1 have been used as biomarkers of exposure to Anopheles mosquito bites. MethodsThis study investigates two novel Anopheles gambiae salivary antigens, AgSAP and SAMSP1, as potential biomarkers of 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. ResultsGSG6-P1, AgSAP, and SAMSP1 levels increased in mice at eight weeks after weekly mosquito feedings. However, human gSG6-P1 and AgSAP levels were paradoxically lower four weeks after direct skin feeding assays. SAMSP1 was the only MSA that induced a significantly higher humoral response during the rainy season, suggesting that it may be a more reliable biomarker for vector exposure in regions with multiple Anopheles species. ConclusionsMosquito salivary antigens associated with Plasmodium infection like AgSAP and SAMSP1 show promise as biomarkers of malaria vector exposure. However, the dynamics of IgG response against AgSAP and SAMSP1 after mosquito bites requires further study.

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