Angewandte Chemie International Edition
© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
For full article and contact information, see Angew. Chem. Int. Ed. 2001, 40 (14), 2631 - 2635
Life-Saving Peptide Ring?
New hope for a malaria vaccine
The danger of being infected with the plasmodium falciparum parasite, the agent that causes the nastiest form of malaria, currently lurks in about one hundred countries. The annual casualty count is estimated to be between 1.5 and 2.7 million. Many strains of plasmodium are already resistant to the medications given for treatment or prevention. Additionally, these agents often have serious side-effects. A vaccine that could offer protection to people in the affected areas is not available. The results of a Colombian-Swiss research collaboration led by Manuel E. Patarroyo now offer new hope.
In order to become immune to an infectious disease, an organism must produce antibodies against the agents, such as bacteria, viruses or parasites, that cause the disease. A vaccine either directly introduces antibodies, or stimulates the immune system to produce the antibodies itself. It has never before been possible to develop a vaccine against diseases caused by parasites.
The malaria parasite goes through a very complex life-cycle between humans and mosquitos. Having been transmitted through a mosquito bite, the parasites nest in the liver of their unwilling host, mature, and flow into the bloodstream. Further stages of development occur within the red blood cells. The blood cells are destroyed - causing a fever. The newly freed parasites then attack more red blood cells, resulting in another fever.
In order to get into the blood cells, the malaria parasites first have to dock on the cells’ membranes - using the MSP-1 protein that sits on the invader’s surface. This could be their weak point: Patarroyo and his co-workers have been able to synthesize a short peptide sequence that is very similar to the MSP-1 binding site. The crucial trick is that they made ring-shaped versions of this peptide chain. "Cyclic peptides are more stable than linear chains, which are very quickly dismantled by enzymes in blood serum," explains Patarroyo. "Ring-closure also makes it possible to fix the peptide in the desired spacial structure."
The researchers successfully immunized apes with the cyclic peptides; the animals developed antibodies. And these antibodies did not just react to their original target, the peptide ring, but also attached themselves to the MSP-1 surface protein on the malaria parasites. This discovery opens up the possibility that a vaccine against malaria can finally be developed in this way.