Shape of things to comeBeating mosquitoes at their own game

Published 23 March 2010

Japanese researchers came up with a brilliant idea: why not use mosquitoes as “flying vaccinators” or “flying syringes”? 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; it worked

A "flying syringe" // Source: pdchost.com

There are few things more satisfying than beating someone at his own game. Take the case of disease-carrying mosquitoes. Martin Enserink writes in Science that 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 which, when they mate with wild -type counterparts, do not produce viable offspring. That would shrink the population over time.

Now, a new study relies on a very different mechanism: Use mosquitoes to become what the scientists call “flying vaccinators” or “flying syringes.” 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.

The 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 the researchers attached SP15, a candidate vaccine against leishmaniasis, a parasitic disease spread by sand flies that can cause skin sores and organ damage. Enserink writes that, sure enough, the mosquitoes produced SP15 in their saliva, as the team reports in the current issue of Insect Molecular Biology. When the insects were allowed to feast on mice, the mice developed antibodies against SP15.

Antibody levels were not 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 1,500 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.

 

Emily Singer writes in Technology Review that it is not yet clear whether the immune response was strong enough to protect against infection. Still, “Following bites, protective immune responses are induced, just like a conventional vaccination but with no pain and no cost,” said Yoshida. “What’s more continuous exposure to bites will maintain high levels of protective immunity, through natural boosting, for a life time. So the insect shifts from being a pest to being beneficial.”

Other researchers are impressed with 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.”

<>For the time being, the idea may well remain more of a proof of principle experiment than a viable public health option. According to an article on ScienceNow,

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.