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Saturday, January 21, 2012

New fronts in the war against malaria

Over the past year, there’s been some encouraging work done on preventing malaria, a disease caused by a parasitic protozoan (Plasmodium) with a complicated lifecycle involving both human and mosquito hosts (see video below).

Here are just three of the many drug or vaccine targets under current investigation, all involving Plasmodium falciparum, the species responsible for the most lethal form of malaria.  Nine out of ten of the hundreds of thousands of annual malarial deaths can be attributed to this little pest.

Joseph Jez of Washington University and his colleagues have isolated a membrane protein (phosphoethanolamine methyltransferase, or PfPMT) that is critical for the growth and survival of P. falciparum within human blood cells. Not only did Jez and his team isolate the protein, but they were also able to determine its exact structure and function. Even more importantly, this particular protein is not found in mammals, making it an ideal drug target. 

University of Oxford biologists led by Alexander Douglas have identified a different blood-stage antigen (reticulocyte-binding protein homologue 5, or RH5) that, unlike most of the other P. falciparum proteins, is highly conserved among all strains of the protozoa.  This means that an immune response generated against this protein should be effective against all strains of the bug.  Scientists have begun testing a vaccine against this particular protein with promising results thus far. 

Finally, David Cavanagh and his colleagues from the University of Edinburgh chose to focus on merozoite surface protein 1 (MSP-1), a protein that makes up about 40% of the surface area of the merozoite life stage of P. falciparum.  Because MSP-1 is highly variable the researchers constructed an artificial gene containing elements from all the major types of the proteins.  In animal tests, this elongated hybrid protein produced a good immune response.