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Engineering mosquitos to reject malaria

Pests that carry a human antibody make poor hosts for parasites.

Engineering mosquitos to reject malaria

One of the easiest and often most effective means of controlling the spread of malaria is to control the mosquitos that carry it to humans. Unfortunately, that has proven to be just as much of an evolutionary arms race as targeting malaria itself; mosquitos evolve resistance to pesticides almost as quickly as malaria has evolved resistance to drugs.

Recent efforts have focused on forms of control that don't impose a huge fitness burden on the mosquito population. This general approach has been tested in the wild on the mosquitos that carry Dengue fever, which scientists infected with bacteria that block the spread of the virus. Now, researchers are reporting that they've developed genetically modified mosquitos that turn mosquitos into a dead-end for the malarial parasite. Their method: have the mosquitos express antibodies against the parasite whenever it feeds on blood.

Antibodies have a relatively poor history when it comes to targeting malaria in humans. Vaccines against the parasite tend to be ineffective, because Plasmodium falciparum has evolved ways of evading an immune response, often completely changing the proteins that coat its surface in order to keep antibodies from recognizing it. But these changes are only triggered once the parasite is already inside the human body.

The mosquito, in contrast, does not have an antibody-based immune response, meaning the parasite hasn't needed to perform the same sort of tricks during that stage of its life cycle. So, the authors used a series of antibodies that recognized proteins specific to the malarial stage that inhabits the insect salivary gland.

Antibodies are normally a complex of four proteins (two heavy and two light chains). To avoid having to put the genes for the full complex in, the authors generated a compact version of the antibody as a single gene that combines sections of the heavy and light proteins. They then inserted two of these compact antibody genes at several locations within the genome. To limit the impact of the antibodies on the mosquitos, the antibody genes were engineered to only come on once after the mosquito had its first blood meal.

From the perspective of not harming the mosquitos, it all seemed to work. Females appeared to be completely unaffected by the inserted genes, and males had only slightly reduced lifespans, which came well after their peak period of fertility. From the mosquito's perspective, the antibody genes don't seem to do it significant harm, so won't cause any sort of selective pressure to get rid of them.

And, to a large extent, they did what they were designed to do, turning the mosquito into a bit of a malarial hotel: the parasites checked in, but couldn't get back out. P. falciparum went about its normal business, but then couldn't manage to make its way into the salivary gland, where it needs to be to spread to other organisms. This should, in theory, mean that the engineered mosquitos are not very good vectors for malaria. One of their four experimental mosquito populations, however, didn't see as strong an effect, so some work clearly needs to be done to identify what might go wrong, and whether there are ways to work around it.

If this really does pan out, then it might be possible to introduce the antibody to mosquito populations in the wild by growing and releasing lots of genetically modified males over the span of several years. Given that the genes don't confer any benefits on the mosquitos, we'd have to continue to supply them to keep them from being lost. But that still might be easier than running other long-term control measures, especially those designed to avoid generating further insecticide resistance.

PNAS, 2012. DOI: 10.1073/pnas.1207738109  (About DOIs).

Channel Ars Technica