Researchers Turn Mosquitoes Into Flying Vaccinators

Nov. 19, 2010, 9:18 a.m.

By Martin Enserink on 18 March 2010
From foe to friend? Transgenic Anopheles stephensi mosquitoes produce a vaccine in their saliva.
Credit: CDC

Here's a study to file under "unworkable but very cool." A group of Japanese researchers has developed a mosquito that spreads vaccine instead of disease. Even the researchers admit, however, that regulatory and ethical problems will prevent the critters from ever taking wing—at least for the delivery of human vaccines.

Scientists have dreamed up various ways to tinker with insects' DNA to fight disease. One option is to create strains of mosquitoes that are resistant to infections with parasites or viruses, or that are unable to pass the pathogens on to humans. These would somehow have to replace the natural, disease-bearing mosquitoes, which is a tall order. Another strategy closer to becoming reality is to release transgenic mosquitoes that, when they mate with wild-type counterparts, don't produce viable offspring. That would shrink the population over time.

The new study relies on a very different mechanism: Use mosquitoes to become what the scientists call "flying vaccinators." Normally, when mosquitoes bite, they inject a tiny drop of saliva that prevents the host's blood from clotting. The Japanese group decided to add an antigen-a compound that triggers an immune response-to the mix of proteins in the insect's saliva.

A group by led by molecular geneticist Shigeto Yoshida of Jichi Medical University in Tochigi, Japan, identified a region in the genome of Anopheles stephensi-a malaria mosquito-called a promoter that turns on genes only in the insects' saliva. To this promoter they attached SP15, a candidate vaccine against leishmaniasis, a parasitic disease spread by sand flies that can cause skin sores and organ damage. Sure enough, the mosquitoes produced SP15 in their saliva, the team reports in the current issue of Insect Molecular Biology. And when the insects were allowed to feast on mice, the mice developed antibodies against SP15.

Antibody levels weren't very high, and the team has yet to test whether they protect the rodents against the disease. (Only very few labs have the facilities for so-called challenge studies with that disease, says Yoshida.) In the experiment, mice were bitten some 1500 times on average; that may seem very high, but studies show that in places where malaria is rampant, people get bitten more than 100 times a night, Yoshida points out. In the meantime, the group has also made mosquitoes produce a candidate malaria vaccine.

Other researchers are wowed by the achievement. "The science is really beautiful," says Jesus Valenzuela of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, who developed the SP15 vaccine. David O'Brochta, an insect molecular geneticist at the University of Maryland, College Park, calls it "a fascinating proof of concept."

So why won't it fly? There's a huge variation in the number of mosquito bites one person received compared with the next, so people exposed to the transgenic mosquitoes would get vastly different doses of the vaccine; it would be a bit like giving some people one measles jab and others 500 of them. No regulatory agency would sign off on that, says molecular biologist Robert Sinden of Imperial College London. Releasing the mosquitoes would also mean vaccinating people without their informed consent, an ethical no-no. Yoshida concedes that the mosquito would be "unacceptable" as a human vaccine-delivery mechanism.

However, flying vaccinators-or "flying syringes" as some have dubbed them -may have potential in fighting animal disease, says O'Brochta. Animals don't need to give their consent, and the variable dosage would be less of a concern.

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