Photo courtesy of the CDC
Recent progress in halting the spread of malaria has hinged, in part, on the use of insecticide-treated bed nets and spraying programs that target Anopheles gambiae mosquitoes.
Unfortunately, the mosquitoes are developing resistance to insecticides such as pyrethroid.
Wondering if they could defeat the mosquitoes by developing a new insecticide,a group of researchers set out to make blood meals toxic for Anopheles gambiae.
The team described their method in The Journal of Experimental Biology.
The researchers decided to target the mosquito glutamate gated chloride channel (AgGluCl), which is an essential component of the insect’s nervous system.
They generated antibodies that specifically targeted a portion of the protein exposed on the surface of nerves, a strategy they acknowledged was somewhat risky.
“Antibodies against a single mosquito antigen have never been shown to have mosquitocidal properties before, and the majority of previous research had focused on midgut antigens, while we were targeting a neuronal antigen expressed only in tissues found outside of the midgut,” said study author Jacob Meyers, a graduate student at Colorado State University in Fort Collins.
After injecting rabbits with a tiny portion of the surface of the AgGluCl protein channel, the researchers waited for the rabbits’ immune systems to begin producing antibodies tailored to the channel.
Then, the team collected the antibodies, mixed them with fresh blood, and fed the mixture to malaria-carrying mosquitoes (Anopheles gambiae), yellow fever-carrying mosquitoes (Aedes aegypti), and mosquitoes that carry the West Nile virus (Culex tarsalis).
Neither the yellow fever nor West Nile virus mosquitoes responded to the spiked blood. However, significant numbers of Anopheles gambiae mosquitoes died after consuming the blood/antibody cocktail. The highest antibody doses killed more than 90% of the insects within a day.
The researchers looked into why the yellow fever and West Nile virus mosquitoes had been immune to the antibodies and found the antibodies could not pass across the mosquitoes’ guts into the hemolymph. But the antibodies passed into the hemolymph of Anopheles gambiae mosquitoes with ease.
Intrigued by the antibodies’ mode of action, the researchers fed the insects a blood meal laced with the antibodies and a lethal dose of ivermectin, an insecticide that also targets the AgGluCl protein channel.
Then, the team monitored the mosquitoes’ survival to find out more about how the antibodies may destroy the insects. Mosquitoes that received ivermectin with the antibodies were more likely to survive than insects that received ivermectin alone.
“We believe that ivermectin is able to bind to AgGluCl,” Meyers said, “but the antibody keeps the channel from opening and becoming active.”
Having shown that antibodies targeted to the glutamate gated chloride channel in blood meals can be effective insecticides, the researchers are interested to find out if antibody-laced blood meals are equally deadly outside the lab.
First, though, the team plans to immunize cattle against the AgGluCl antigen and feed Anopheles gambiae on the immunized cattle in the lab. If the strategy proves successful, Meyers envisages a large-scale cattle immunization program as part of a combined attack on the malaria parasite.
