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Mosquitoes against malaria?

Anopheles_albimanus_mosquitosmall.jpgTwo malaria papers out this week in the New England Journal of Medicine have seen some press coverage. Undoubtedly the more concerning discusses the parasite’s increasing resistance to artemisinin-based drugs in Cambodia – see Nature’s news story.

The other, as Carlos Campbell of the PATH malaria vaccine initiative writes in an accompanying editorial, “reminds us that the whole malaria parasite is the most potent immunizing antigen identified to date”. In what AP describe as a “daring experiment” with “astounding” results, researchers found that ten people subjected to mosquito bites three times over three months whilst taking the drug chloroquine gained apparent immunity against malarial mosquito bites a month later.

It’s hard to see, however, that this finding adds much new to the vaccine-hunter’s arsenal.

It’s been known since the 1960s that sporozoites, cells that travel from the insect’s salivary gland to the bitten human’s liver can help provide immunity (which is why the first bout of malaria is usually the worst). This study has confirmed that. The difficulty is using this tactic to actually immunize patients – producing whole sporozoites for a real vaccine requires the breeding of many live mosquitoes and human blood to test on. As Campbell adds in his editorial, the carefully timed and controlled mosquito-inoculation approach, so far removed from the real world, “cannot be the basis for a human malaria vaccine”.

Right now, though, production of irradiated and weakened sporozoites – garnered from irradiated mosquitoes – is ongoing [AP, pdf] for injection in first-stage (safety) human trials at Maryland-based biotech company Sanaria (an effort that has taken over three decades). Meanwhile, in a PNAS paper last week which did not go through a rigorous peer review procedure, a collaboration of researchers reported that human trials would begin in early 2010 for another similar approach: this time weakening the sporozoite by snipping out two genes, rather than irradiating malaria.

Other malaria vaccine trials are based on using protein fragments, rather than the whole sporozoite to induce immunity. These include Glaxo’s RTS,S phase III trials which began a few months ago; while Dutch pharmaceutical company Crucell recently announced a collaboration with the PATH malaria vaccine initiative, to use adenoviruses to deliver a malaria antigen to the immune system. (The MVI has a full list of malaria vaccines in development).

image: James Gathany/CDC


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