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.
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.
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