Blood-stage immunity to Plasmodium chabaudi malaria following chemoprophylaxis and sporozoite immunization

Malaria is a life-threatening infectious disease in humans that is caused by a single-celled parasite called Plasmodium. The parasite is carried between people by mosquitos; when an infected mosquito bites a human, the parasite is injected into the bloodstream with the mosquito's saliva. Plasmodium first infects liver cells but then re-enters the bloodstream, where it infects red blood cells leading to symptoms of disease. If another mosquito bites the infected individual at this so-called ‘blood-stage’, the parasite can be passed to this mosquito and the cycle of transmission continues. Currently there are no vaccines available that can effectively protect against malaria. Although an experimental vaccine containing a weakened form of the parasite can protect against the liver-stage parasites, it fails to prevent the parasite from multiplying in the red blood cells. Therefore, the individuals remain susceptible to severe malaria. Recently, researchers have developed a new strategy for immunization that provides exposure to both liver-stage and blood-stage parasites. Human volunteers taking an anti-malarial drug were deliberately exposed to mosquitos carrying the parasite on three separate occasions. Although the volunteers were infected with the parasite, the anti-malarial drug killed the parasites inside the red blood cells. After the end of the drug treatment, the volunteers were exposed to mosquitos carrying the parasite and they were still protected from infection. These results are promising, but it is not clear if the volunteers have acquired immunity to liver-stage or blood-stage parasites, or even both. To answer this important question, Nahrendorf et al. developed a similar immunization strategy in mice. Just like the human volunteers, the mice were treated with an anti-malarial drug and exposed to mosquitos carrying Plasmodium on three separate occasions. Although the immunizations did not protect the mice against early infection in the liver, they did provide long-term protection against parasites multiplying in the red-blood cells. The immunity generated by this immunization strategy also protected the mice against another strain of Plasmodium, different to the one used in the immunizations. The experiments also show that prolonged exposure to the blood-stage parasites can even lead to immunity against the liver-stage parasites. Nahrendorf et al.'s findings show that this immunization strategy can protect individuals against both the liver-stage and blood-stage parasites. The next challenges are to find out how the immunity generated by one stage of infection can protect against the other stages, and to discover which molecules on the parasite the immune system targets.