Vaccine makes blood toxic to mosquitoes

April 14, 2003 at 6:27 PM
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FORT COLLINS, Colo., April 14 (UPI) -- Experiments reveal that vaccines might one day make human blood lethal to mosquitoes.

While the scientists developing the vaccine stress their findings in mice are only preliminary, they hope future vaccines could help radically stem the growing tides of malaria and other dangerous mosquito-borne infections.

"Control the mosquito and its biting, and you can start controlling the disease," lead researcher Brian Foy, a molecular biologist and entomologist at Colorado State University in Fort Collins, Colo., told United Press International.

Malaria alone kills anywhere from 1 million to 3 million people a year worldwide -- mostly children and pregnant women.

When it comes to combating any insect-borne disease, the most successful weapons thus far are pesticides such as DDT, which kill or drive off the germ's hosts. Unfortunately, pesticides are growing increasingly useless as insects become more and more resistant. Given that these toxins are also environmentally hazardous and increasingly expensive, medical authorities are urgently seeking alternatives.

For decades, scientists have experimented with immunizing humans not only against insect-borne germs such as malaria and Lyme disease, but against the mosquitoes, ticks and other bloodsuckers themselves. For instance, priming the body's defenses against proteins in the saliva of the sandfly could help neutralize the potentially lethal Leishmaniasis parasite also found in the fly's spit, Foy said.

Foy and colleagues chose the mosquito Anopheles gambiae as their target. This creature loves biting humans, with each female drinking the blood of 10 or more during its lifetime for proteins to help their eggs grow. And of course, their bites are more than mere annoyances -- these bloodsuckers are infested with protozoa that cause malaria as well.

Malaria parasites will most likely infect a person only after a mosquito has had between four and 12 blood meals, since it takes about two weeks, once the insect starts feeding, for malaria germs to become infectious. This means human blood that could kill an infected mosquito early on would stand a high chance of stopping the disease in its tracks altogether.

"We are trying to lay the scientific groundwork for a vaccine that would kill the biting mosquito before she could transmit the malaria parasite," Foy said.

A key target has always been the insect's midgut, where blood is stored and digested. In Australia, a vaccine now used against cattle ticks reveals how a similar mosquito-killing therapy could work. Cows given injections of tick gut proteins develop antibodies, cells and other immune defenses in their bloodstream that, when sucked up by infesting ticks, mob target proteins and rip the innards of the parasites apart.

Unfortunately, identifying just one of these protein targets in ticks took four years, since scientists had to laboriously extract kilograms worth of tick guts and purify them for the proteins. This method becomes nearly impossible when dealing with smaller germ-carriers like mosquitoes.

"It is very difficult to dissect hundreds of mosquito midguts in the first place, but even harder to separate the thousands of different proteins from dissected midgut tissue while keeping them in their natural shape and making them relatively pure from each other," Foy said.

Researchers have tried injecting mice and rabbits with a slew of mosquito juices, with ambiguous mosquito-killing results. Instead of relying on the lengthy process of mosquito dissection just to get a crude mix of proteins at the end, Foy and colleagues used the genes for these proteins. Cells absorb injected DNA and manufacture the protein themselves. The researchers can synthesize DNA within a day, and in this simpler fashion methodically test molecules one at a time to see which ones were most effective in vaccines.

The researchers vaccinated the mice with the DNA encoding a sugary protein known as mucin, found coating the midgut surface of the mosquito. In findings appearing in the April issue of the journal Infection and Immunity, the researchers found mosquitoes biting vaccinated mice were nearly twice as likely to be dead after a week's time than mosquitoes attacking unvaccinated mice.

"A number of people have tried to vaccinate against mosquitoes, but these are the best results so far," vaccine developer and biochemist Peter Willadsen of Australia's Commonwealth Scientific and Industrial Research Organization (CSIRO) in St. Lucia told United Press International.

"The obvious criticism is that the effects on mosquito mortality, though significant, take some time to work and are a lot less than 100 percent effective. So this is not a 'cure for malaria,'" Willadsen added. "Such a criticism would be pretty unfair -- this is then first step on what is potentially a very long road to a practical outcome, but an encouraging one nevertheless."

When mosquitoes drank serum made from the blood from vaccinated mice -- serum that had had all the mouse blood cells removed -- the serum alone did not increase mosquito death rate. While this broadly hints that white cells in the blood of the vaccinated mice were driving mosquito deaths, that idea "is too vague for my liking now. I'd like to understand more precisely why the mosquitoes die, which immune cells are contributing to the death, and how. We are in the process of examining these questions," Foy said.

Immunologist Stephen Wikel at the University of Connecticut Health Center in Farmington agreed that understanding the specific details of the immune response was crucial. "You want to avoid something that isn't protective, such as stimulating an allergic response or anything like that.

While this strategy could work very well against malaria, Foy cautioned West Nile virus was probably not as good a target, since its mosquito host bit animals other than humans as well. "You can't vaccinate all the animals that get West Nile," he said.

Dengue fever, which attacks 50 million to 100 million annually and is carried by another human-hungry pest, might be a possibility, but "there are huge differences. Malaria's caused by a parasite and dengue by a virus, for one thing. And they rely on a completely different species as well, named Aedes aegypti," Foy explained.

In the end, Foy has "no doubt" that research will turn up other, better molecular targets in mosquitoes. While he believes mosquitoes will in time evolve resistance against this vaccine just as they would against any other insecticide, "nobody talks about a single magic bullet anymore to control malaria. You can't just have one weapon and employ it by itself," Foy said.

"Instead, you need to have an arsenal of weapons, and you need to employ them all at once and consistently," he added. He looks forward, for instance, to his team's research going hand in hand with the ongoing search for a vaccine against the malaria parasite itself.

(Reported by Charles Choi, UPI Science News, in New York.)

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