Abstract
BackgroundMalaria is transmitted when infected Anopheles mosquitoes take a blood meal. During this process, the mosquitoes inject a cocktail of bioactive proteins that elicit antibody responses in humans and could be used as biomarkers of exposure to mosquito bites. This study evaluated the utility of IgG responses to members of the Anopheles gambiae D7 protein family as serological markers of human–vector contact.MethodsThe D7L2, D7r1, D7r2, D7r3, D7r4 and SG6 salivary proteins from An. gambiae were expressed as recombinant antigens in Escherichia coli. Antibody responses to the salivary proteins were compared in Europeans with no prior exposure to malaria and lifelong residents of Junju in Kenya and Kitgum in Uganda where the intensity of malaria transmission is moderate and high, respectively. In addition, to evaluate the feasibility of using anti-D7 IgG responses as a tool to evaluate the impact of vector control interventions, we compared responses between individuals using insecticide-treated bednets to those who did not in Junju, Kenya where bednet data were available.ResultsWe show that both the long and short forms of the D7 salivary gland antigens elicit a strong antibody response in humans. IgG responses against the D7 antigens reflected the transmission intensities of the three study areas, with the highest to lowest responses observed in Kitgum (northern Uganda), Junju (Kenya) and malaria-naïve Europeans, respectively. Specifically, the long form D7L2 induced an IgG antibody response that increased with age and that was lower in individuals who slept under a bednet, indicating its potential as a serological tool for estimating human–vector contact and monitoring the effectiveness of vector control interventions.ConclusionsThis study reveals that D7L2 salivary antigen has great potential as a biomarker of exposure to mosquito bites and as a tool for assessing the efficacy of vector control strategies such as bednet use.Graphical abstract
Highlights
Malaria is transmitted when infected Anopheles mosquitoes take a blood meal
Feasibility studies carried out show that children resident in an area with seasonal malaria transmission developed anti-mosquito saliva immunoglobulin G (IgG) that was correlated with mosquito density [2] and that declined rapidly upon introduction of insecticide-treated bednets [3]
The predicted sizes of the recombinant mosquito salivary antigens were as follows: D7r1 (18 kDa), D7r2 (18 kDa), D7r3 ( 18 kDa), D7r4 (19 kDa), gambiae salivary gland protein 6 (gSG6) (13 kDa) and D7L2 (36 kDa), corresponding to the protein bands observed after purification (Fig. 1)
Summary
Malaria is transmitted when infected Anopheles mosquitoes take a blood meal. During this process, the mosquitoes inject a cocktail of bioactive proteins that elicit antibody responses in humans and could be used as biomarkers of exposure to mosquito bites. The human host mounts an immune response to the mosquito salivary components to counteract its effects. The levels of anti-mosquito saliva antibodies can possibly reflect the extent of human exposure to mosquito bites at the individual and population levels. Feasibility studies carried out show that children resident in an area with seasonal malaria transmission developed anti-mosquito saliva immunoglobulin G (IgG) that was correlated with mosquito density [2] and that declined rapidly upon introduction of insecticide-treated bednets [3]
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