According to a new study published in the open-access journal PLoS Pathogens, Dutch researchers have identified and characterized several parasite proteins that potentially may be used to design a human malaria vaccine.

Africa loses 2000 children every day from malaria, a disease that humans contract from mosquitoes. Mosquitoes spread the disease from human to human each time they take a blood meal from an infected person and follow it with a blood meal from an uninfected person (who then becomes infected). A vaccine is has not yet been developed, although there is a large research effort supporting it.

The mosquito injects protozoan parasites that migrate to the liver and mature there. After maturing, infective cells (sporozoites) travel throughout the body via the bloodstream, which leads to disease and fatal complications. Researchers are working on a vaccination strategy based on weakening the parasites so that they invade liver cells, stimulate an immune response, and then stop developing. If the vaccine can deactivate individual genes that are active while the parasite is growing in the liver, it should be successful. Dr. Edwin Lasonder (Department of Molecular Biology, NCMLS, Radboud University Nijmegen, Nijmegen, The Netherlands) and colleagues were able to modify the proteins that are necessary for this sporozoite development that infects the liver.

Previous research has demonstrated that removing one of these liver genes (p36p) in rodent malaria was a successful way to vaccinate mice. Transitioning this rodent vaccination to humans, as described in a paper published in the October 28th issue of PLoS ONE, can be achieved by inactivating the equivalent gene (p52) in P. falciparum – the major human malaria parasite.

According to the article, genetic modification of a human parasite followed by growth arrest in a liver cell has never occurred before. The studies demonstrate great promise for a human vaccine, and they demonstrate the utility of rodent models can form the basis for clinical development of anti-malaria vaccines in humans.

Proteomic Profiling of Plasmodium Sporozoite Maturation Identifies New Proteins Essential for Parasite Development and Infectivity
Lasonder E, Janse CJ, van Gemert G-J, Mair GR, Vermunt AMW, et al.
PLoS Pathogens (2008). 4(10):e1000195.
doi:10.1371/journal.ppat.1000195
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Written by: Peter M Crosta